What is a neurotransmitter?

A neurotransmitter is an intercellular messenger molecule. It is generated in and released by a presynaptic neuron, and it acts on an adjacent postsynaptic neuron or neuroeffector cell, or even back on the neuron that released the molecule. With this definition, we can distinguish two classes of chemical neurotransmitter substances: conventional and unconventional transmitters.

Conventional neurotransmitters comprise three groups

All conventional neurotransmitters are stored in synaptic vesicles (SVs) and are released in quantal fashion by Ca ²⁺ -dependent exocytosis. These conventional transmitters can be divided into three groups. One group includes ACh, γ-aminobutyric acid (GABA) , glutamate, glycine ( Fig. 13.1 ), and certain purines. They are stored in approximately 40-nm diameter, electron-lucent SVs. These transmitters are released and act at well-defined synapses with “classical” structures: the presynaptic cells, which have active zone densities in their boutons, are separated by narrow (20- to 40-nm) synaptic clefts from the postsynaptic cells, which have specialized postsynaptic densities ( Fig. 12.3 ). This type of synaptic transmission is sometimes referred to as wiring transmission because direct connection of presynaptic and postsynaptic cells can be viewed as “hard wiring.” Transmission at electrical synapses ( Chapter 12 ) also is a type of wiring transmission.

The Structures of Some Common Neurotransmitters.

Acetylcholine is synthesized from choline and acetyl-coenzyme A; γ-aminobutyric acid (GABA) is synthesized from glutamate; serotonin (5-HT) is derived from tryptophan; histamine is derived from histidine; and the catecholamines (dopamine, epinephrine, and norepinephrine) are sequentially derived from tyrosine. The following conventions have been used in these structural drawings: (1) implicit carbon: every unlabeled vertex, whether internal or terminal, represents a carbon atom; (2) implicit hydrogen: every carbon has a sufficient number of (undrawn) hydrogens to make the total number of bonds to that carbon equal to 4; and (3) explicit heteroatoms: noncarbon, nonhydrogen atoms (e.g., O, N) are labeled explicitly; hydrogens attached to the heteroatom are also explicitly drawn. For example, is equivalent to CH ₃ -CH = CH-CH ₂ -OH. In addition, a solid wedge bond means the attached group extends above the plane of the page; a hatched bond means the attached group extends below the plane of the page.

A second group of conventional neurotransmitters comprises biogenic monoamines : serotonin (5-hydroxytryptamine or 5-HT), histamine , and the catecholamines ^a

a Catecholamines all contain a catechol (1,2-dihydroxybenzene) moiety.

(dopamine, norepinephrine [NE], and epinephrine [Epi], which are sequentially derived from tyrosine) ( Fig. 13.1 ). These transmitters are usually stored in small dense-core (electron-opaque) SVs, which are approximately 40 to 70 nm in diameter. Biogenic amines can be released at classical synapses where the closely apposed postsynaptic cells have specialized postsynaptic densities. Biogenic amine transmitters are also released at en passant synapses where the presynaptic “terminals” are simply SV-containing varicosities (enlargements) that occur along axons as they pass postsynaptic cells. At en passant synapses, the postsynaptic cells often exhibit typical postsynaptic density regions to which the transmitter receptors are confined. In many instances, however, the transmitter receptors are more diffusely distributed on the postsynaptic cell surface. A good example of the latter is the synapse between a sympathetic neuron and a vascular smooth muscle cell.

At en passant synapses, the released transmitter may activate several postsynaptic cells. This type of neurotransmission is sometimes referred to as volume transmission , because the transmitter activates all postsynaptic cells that express the appropriate receptor within the volume of tissue in which the transmitter concentration is sufficiently high. In contrast to the situation at classical synapses, neurotransmitters must diffuse across greater distances to reach postsynaptic cells; hence the synaptic delay is correspondingly longer for volume transmission.

The third group of conventional transmitters, the neuropeptides, range in length from 3 to approximately 100 amino acid residues, although most have fewer than 30 residues. These peptide neurotransmitters are often stored in large dense-core vesicles (∼100–150 nm diameter) in which monoamines are frequently cosequestered. These SVs are often concentrated in, and release their contents from, boutons at classical synapses. Neuropeptide transmitter release is distinctive in requiring bursts of presynaptic APs, whereas most other conventional transmitters are usually released by a single AP. Ca ²⁺ -evoked release from large dense-core vesicles may also occur at various places along the presynaptic axon where no apparent synaptic structures are present. This type of transmitter release therefore more closely resembles the secretion of most hormones by endocrine cells, which do not have specialized active zones where the secretory vesicles cluster before release. Indeed, the storage and secretion of peptide hormones in the magnocellular neurons (large cell neurons) of the hypothalamus ^b

Roger Guillemin and Andrew Schally shared (with Rosalyn Yalow) the 1977 Nobel Prize in Medicine or Physiology for their discoveries of peptide “releasing” hormones, which are stored in and released by hypothalamic neurons. In 1931, Ulf von Euler first discovered a peptide neurotransmitter, substance P. von Euler and Julius Axelrod did pioneering research on norepinephrine as a neurotransmitter, for which they shared the 1970 Nobel Prize in Medicine or Physiology with Bernard Katz ( Chapter 12 ).

were originally believed to be a peculiarity of these neuroendocrine cells. We now recognize that this phenomenon is much more widespread in the nervous system.

Conventional neurotransmitters activate two classes of receptors: Ionotropic receptors and metabotropic receptors

Metabotropic receptors are not ion channels but are proteins with seven transmembrane helices

Binding of a neurotransmitter activates a metabotropic receptor, which in turn activates a G-protein . These receptors are therefore members of the G-protein–coupled receptor (GPCR) family. ^c

Alfred G. Gilman and Martin Rodbell were awarded the 1994 Nobel Prize for Physiology or Medicine for discovering G-proteins and characterizing their role in cell signaling.

This is the largest family of membrane proteins in the human genome; its members influence almost all biological responses and are the targets of approximately 60% of clinically useful drugs. Most metabotropic receptors function as homodimers or heterodimers (or even oligomers). Binding of a neurotransmitter molecule to one monomer is usually sufficient to activate the dimer fully, and binding of a transmitter molecule to the second monomer may even reduce the activity of the dimer.

A G-protein is a heterotrimeric protein complex comprising α-, β-, and γ-subunits; the α-subunit has a binding site for guanine nucleotide . A wide range of different α-, β-, and γ-subunits is expressed, giving rise to many possible αβγ trimer combinations that can couple diverse receptors to downstream effectors ( Fig. 13.2 ). In the quiescent state, a guanosine diphosphate (GDP) is bound to the α-subunit of a G-protein (α _GDP βγ). Some α _GDP βγ complexes are bound to appropriate GPCR dimers, thus forming inactive pentameric complexes. On activation by a neurotransmitter molecule, the metabotropic receptor catalyzes the exchange of guanosine triphosphate (GTP) for GDP to generate α _GTP βγ. This enables the α _GTP βγ complexes to dissociate into α _GTP and βγ moieties, each of which can interact with downstream effectors such as phospholipase C, protein kinase C (PKC), or adenylyl cyclase, to initiate a cellular response ( Fig. 13.2 ). The signal is terminated when the α-subunit hydrolyzes the bound GTP, causing the reversion to α _GDP , which then can recombine with βγ to regenerate the inactive α _GDP βγ trimer. Because G-protein signaling depends on multiple enzymatic processes, synaptic responses mediated by metabotropic receptors are necessarily slower than those mediated by ionotropic receptors.

The Agonist Receptor–G-Protein–Phosphoinositide Cascade.

The diagram shows the sequence of events that occurs after the binding of an agonist to its G-protein–coupled receptor in the plasma membrane. In the example illustrated here, NE activates a vascular smooth muscle α ₁ -adrenergic receptor (α ₁ AR). The activated α ₁ AR promotes exchange of GTP for GDP on a heterotrimeric G-protein and its subsequent dissociation into α _GTP and βγ complexes. The α _GTP activates phospholipase C (PLC) , which catalyzes the cleavage of the membrane lipid, phosphatidylinositol 3,4-bisphosphate (PIP ₂ ) into two second messengers. One of these is inositol 1,4,5-trisphosphate (IP ₃ ) , which binds to endo/sarcoplasmic reticulum IP ₃ receptors (IP ₃ Rs)/Ca ²⁺ channels and triggers the release of Ca ²⁺ from the ER or SR. The other is diacylglycerol (DAG) , which can trigger the entry of Ca ²⁺ from the extracellular fluid through receptor-operated channels (ROCs) , as well as stimulate protein kinase C (PKC) to phosphorylate downstream signaling proteins. Although not shown here, the βγ complex may also interact with downstream effector mechanisms.

Metabotropic receptor–coupled G-proteins are molecular switches that modulate postsynaptic activity in a variety of ways. For example, the α-subunit of G-proteins activates enzymes that generate second messengers such as inositol trisphosphate (IP ₃ ), diacylglycerol (DAG) ( Fig. 13.2 ), and the cyclic mononucleotides , cAMP and cGMP. The IP ₃ releases Ca ²⁺ from the sarcoplasmic reticulum/endoplasmic reticulum (S/ER), and DAG and the cyclic nucleotides can gate ion channels or stimulate protein kinases to phosphorylate other proteins. The βγ subunits can directly modulate Ca ²⁺ channels and K ⁺ channels (e.g., inward rectifier, Kir, channels; Box 8.5 ). Phosphorylation at multiple sites on the cytoplasmic loop of the GPCR regulates its activity. This and the variety of transmitter receptors and their subtypes, and the variety of G-protein subunit isoforms, result in a rich tapestry of responses.

Nicotinic acetylcholine receptors are ionotropic

The nicotine acetylcholine receptor (nAChR) expressed at the neuromuscular junction (NMJ) ( Chapter 12 ) is a representative ionotropic receptor. Five homologous nAChR subunits (α, β, γ, δ, and ε) have been identified. Each nAChR is a pentamer containing at least two α-subunits in combination with other subunits. At the NMJ, the subunit composition is 2α:β:δ:ε; in cholinergic neurons in the brain, the composition is often 3α:2β. Each subunit has five membrane-spanning domains and a large extracellular domain. Transmembrane segments from the five subunits form the channel pore, which opens when each of the two α-subunits binds an ACh molecule simultaneously. Functional characteristics of nAChRs, which are nonselective cation channels, are discussed in a later section. As their name implies, nAChRs also can be activated by the tobacco plant alkaloid ^d

d Alkaloids are nitrogen-containing ringed compounds, usually of plant origin, that have physiological actions on animals and humans.

BOX 13.1

Congenital and Acquired Myasthenic Syndromes Result From Defective Neuromuscular Transmission

Myasthenia gravis is a neuromuscular disease characterized by muscle weakness and fatigability. It almost always affects the eyelids, eye muscles, and limb muscles. The most prevalent form of the disease is the autoimmune form, in which antibodies are produced against nAChRs. These antibodies bind to the α-subunit of the receptor and prevent activation of the receptor by ACh. In addition, the density of nAChRs is reduced in myasthenia gravis. As a result, the amplitude of the EPP is reduced to near threshold and many EPPs fail to activate the muscle, thus accounting for the weakness.

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of disorders caused by presynaptic, synaptic, or postsynaptic defects at the neuromuscular junction. The clinical picture in all forms of these syndromes consists of respiratory and feeding difficulties at birth or weakness of the ocular and bulbar muscles (muscles of the tongue, lips, and pharynx) during the first 2 years of life. Postsynaptic CMS can be associated with changes in the gating kinetics of nAChR channels or with a reduction in the density of nAChR channels in the postsynaptic membrane. In the fast channel syndrome a mutation in the nAChR channel results in a greatly reduced postsynaptic response to ACh. Patch clamp recordings of single nAChR channels reveal that the mutation causes the channel open time to be much shorter than that of wild-type channels ( Fig. 13.3 ). Because of the reduced inward current through ACh-gated channels, many skeletal muscle cells fail to reach AP threshold and thus fail to contract. This results in muscle weakness.

ACh-gated channel openings in a patient with CMS are briefer than normal. Single ACh-gated channel openings (shown as upward deflections) were recorded at an NMJ from a normal individual ( control ) and from a patient with CMS ( patient ). The single channel openings in the patient are briefer and less frequent than in the control subject.

(Data from Ohno, K., Wang, H.L., Milone, M., Bren, N., Brengman, J.M., Nakano, S., Quiram, P., Pruitt, J.N., Sine, S.M., & Engel, A.G. (1996). Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron , 17(1), 157–170.)

The enzyme acetylcholinesterase (AChE), which hydrolyzes ACh into acetate and choline, is highly concentrated in the synaptic cleft at cholinergic synapses, including the NMJ. After the release of ACh, AChE rapidly reduces the extracellular ACh concentration and thereby contributes to the termination of its action. A Na ⁺ -coupled cotransporter retrieves choline back into the presynaptic nerve terminals, where it is used to resynthesize ACh. Some paralytic drugs and toxins, including several clinically useful agents, act through interactions with nAChRs or AChE ( Box 13.2 ).

Muscarinic acetylcholine receptors are metabotropic

Muscarinic AChRs (mAChRs) are GPCRs that mediate most of the actions of ACh in the central nervous system (CNS) . Five mAChR subtypes (M ₁ to M ₅ ) have been identified. The mAChRs are expressed by many CNS neurons and by various effector cells, including cardiac, smooth muscle, vascular endothelial, and exocrine gland cells. Many of these cells express two or more mAChR subtypes; this results in a diverse array of postsynaptic responses. Activation of mAChRs can lead to phosphoinositide hydrolysis and IP ₃ -activated Ca ²⁺ release from the S/ER, to inhibition of adenylyl cyclase and reduction of cAMP levels, or to activation of Kir channels ( Box 8.5 ).

In the brain, activation of M ₁ -, M ₂ -, and M ₅ -mAChRs modulates region-specific release of some neurotransmitters, including ACh (through autoreceptors ), dopamine, and GABA, and inhibition of certain nAChRs. The multiple underlying mechanisms include, among others, the phosphoinositide-Ca ²⁺ -PKC cascade (phosphoinositide cascade ), opening of Kir channels, and protein kinase-mediated modulation of N- and P/Q type voltage-gated Ca ²⁺ channels ( Table 8.2 ). Agonists and antagonists of specific mAChR subtypes have been developed to alleviate symptoms of Alzheimer’s disease and schizophrenia by augmenting and antagonizing cholinergic transmission, respectively.

The mAChRs modulate sympathetic and parasympathetic ganglionic function by altering neuronal excitability. Classic examples of parasympathetic effects are slowing of the heart, contraction of bladder and airway smooth muscles, endothelium-mediated vasodilation, and secretion of fluid and electrolytes by the salivary glands. M ₂ -, M ₃ – and M ₄ -mAChRs mediate cardiac slowing by activating, respectively, a Kir channel and two different slowly-opening voltage-gated K ⁺ channels. The mAChR-triggered, Ca ²⁺ -dependent salivary secretions and bladder and airway smooth muscle contractions are activated, in part, by phospholipase C-mediated generation of IP ₃ and consequent mobilization of Ca ²⁺ from the S/ER ( Fig. 13.2 ).

Muscarinic AChRs are so named because they are activated by muscarine , a toxic alkaloid found in the poisonous mushroom, Amanita muscaria. Muscarine is called a parasympathomimetic agent because it mimics the natural parasympathetic agonist, ACh. Two other toxic alkaloids, atropine , from the deadly nightshade (Atropa belladonna), and scopolamine , from other members of the nightshade plant family, are mAChR antagonists that are employed clinically. Atropine is used routinely in ophthalmology to dilate the pupil of the eye. Atropine blocks mAChRs on the pupillary constrictor muscle; the unopposed dilator muscle, which is activated by NE, then dilates the pupil. Scopolamine, which can cross the blood-brain barrier ( Box 3.5 ), is used to prevent nausea and motion sickness; its mechanism of action is still unresolved.

Glutamate is the main excitatory neurotransmitter in the brain

Glutamate ( Fig. 13.1 ), which acts on both ionotropic and metabotropic glutamate receptors, does not cross the blood-brain barrier and must therefore be synthesized in the brain. The three types of ionotropic glutamate receptors are named for the pharmacological agents that activate them selectively: N -methyl- d -aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors (AMPARs) , and kainate (kainic acid) receptors. The kainate receptors (KARs) and AMPARs are closely related structurally, whereas NMDARs are more distantly related. Ionotropic glutamate receptors are heterotetramers or homotetramers of protein subunits that are expressed as multiple isoforms.

Both NMDARs and AMPARs are expressed at most glutamatergic synapses, but some synapses may express only one receptor type. NMDARs are unusual because their activation requires, in addition to glutamate, a coagonist that is thought to be glycine or d -serine. Full activation requires simultaneous binding of two glutamate and two coagonist molecules. Activation of AMPARs and NMDARs also induces kinetically different synaptic responses. AMPARs are monovalent cation–selective channels that mediate most of the fast excitatory synaptic transmission in the brain. They gate rapidly, are poorly permeable to Ca ²⁺ , desensitize strongly, and are blocked by intracellular polyamines such as spermine and spermidine. In contrast, NMDARs are slower-gating, nonselective cation channels that are permeable to Ca ²⁺ but are blocked by extracellular Mg ²⁺ . The physiological importance of the differences between AMPARs and NMDARs is discussed in a subsequent section.

KARs appear to be more complex. They have ionic conductances similar to those of AMPARs but, like metabotropic receptors, they may also activate intracellular signaling cascades at some synapses. Some KARs are located on presynaptic terminals, where they can facilitate release of neurotransmitters.

There are also three types of metabotropic glutamate receptors (mGluR groups I to III, with a total of eight subtypes). The mGluRs are widely distributed in the brain, on postsynaptic neurons, and on presynaptic terminals where they may modulate transmitter release. Many mGluRs are also expressed in glial cells, where they can be activated to increase [Ca ²⁺ ] _i and open Ca ²⁺ -activated K ⁺ (K _Ca ) channels, and thus change [K ⁺ ] _o in the immediate vicinity of the synapse. The consequent shift in the V _m of the presynaptic terminal may influence transmitter release.

Neuronal mGluRs exert their effects by regulating key intracellular signaling pathways. For example, activation of some group I mGluRs stimulates phospholipase C to augment NMDA-mediated excitation. Conversely, activation of some type II and III mGluRs can reduce excitation by inhibiting adenylyl cyclase. Some mGluRs also modulate synaptic transmission at GABAergic and monoaminergic synapses. Such a broad spectrum of actions results in mGluR involvement in diverse pathophysiological responses including mood disorders, epilepsy, and addictive behavior.

γ-Aminobutyric acid and glycine are the main inhibitory neurotransmitters in the nervous system

Inhibitory synapses that use the amino acids GABA and glycine ( Fig. 13.1 ) as neurotransmitters are the most abundant synapses in the CNS. Most of the neurons that release GABA are interneurons, which are neurons that make short-range connections with other neurons. Whereas GABA is the predominant inhibitory neurotransmitter in the brain, glycine is the main inhibitory neurotransmitter in the spinal cord. Many inhibitory synapses in the spinal cord, and even in the adjacent brainstem and in the cerebellum, however, release both GABA and glycine. The functional significance of this apparent redundancy is unknown.

Two types of GABA receptors, GABA _A R and GABA _C R, and strychnine-sensitive glycine receptors (GlyR) ( Box 13.3 ) are ionotropic receptors. These receptors are all pentameric transmitter-gated Cl ⁻ channels. Reduced inhibitory synaptic transmission, in some cases the result of a genetic GlyR defect, is responsible for human startle disease ( Box 13.3 ).

GABA _A Rs are activated by the cooperative binding of two GABA molecules. GABA _A Rs are also the target of benzodiazepines, agents such as diazepam (Valium) and chlordiazepoxide (Librium), which are widely used to treat anxiety disorders. These drugs bind to the GABA _A Rs and potentiate the action of GABA.

There also are metabotropic inhibitory transmitter receptors: the GABA _B Rs. Activation of GABA _B Rs stimulates second messenger systems involving phospholipase C and adenylyl cyclase and leads to the opening of K ⁺ channels or inhibition of Ca ²⁺ channels. Both mechanisms generate slow inhibitory signals in the postsynaptic neurons. When GABA _B Rs are located on presynaptic terminals (as they often are), their activation inhibits transmitter release.

At excitatory synapses, the reversal potential is more positive than the action potential threshold

In Chapter 12 , synaptic transmission at the NMJ, a well-studied excitatory synapse, was described by the following sequence of events: A presynaptic AP releases ACh molecules, which diffuse across the synaptic cleft and bind to nAChRs. This opens the nAChR channels and depolarizes the postsynaptic membrane.

When an nAChR channel opens near the resting V _m , inward current flows through the open channel. In response to a presynaptic AP at the NMJ, millions of molecules of ACh are released, and they cause a large number of nAChR channels to open nearly synchronously. The macroscopic (whole-cell) current through these open nAChRs is called the end-plate current (EPC) . The inward EPC causes the muscle membrane to depolarize, thereby producing the end-plate potential (EPP) described in Chapter 12 ( Fig. 12.5 ).

The ionic species that flow through an open nAChR channel can be identified using a voltage clamp to characterize the effect of V _m on the amplitude of the EPC. When the postsynaptic V _m is made less negative, in the range of –100 mV to –20 mV, the amplitude of the inward EPC becomes smaller ( Fig. 13.4 ). When V _m ≈ 0 mV, there is no detectable EPC (i.e., its amplitude is 0); at more positive membrane potentials the EPC is outward rather than inward ( Fig. 13.4 ). The V _m at which the EPC reverses direction from inward to outward is called the reversal potential ( E _rev ; Chapter 6 ). If Na ⁺ movements were solely responsible for generating the EPC, E _rev would be equal to E _Na . In fact, at the NMJ E _rev is approximately 0 mV, which is much more negative than E _Na and far from the equilibrium potential for any ion. This implies that more than one ionic species moves through the open nAChR channel; indeed, these channels are almost equally permeable to Na ⁺ and K ⁺ . When the channel opens near the normal resting potential, the current direction is inward because K ⁺ is close to equilibrium (i.e., V _m ≈ E _K ) so that there is little K ⁺ efflux. However, a large Na ⁺ influx results from the large inward driving force on Na ⁺ (i.e., V _m – E _Na << 0). The resulting inward EPC depolarizes the membrane to the AP threshold (∼ −45 mV). Indeed, a general characteristic of all excitatory synapses is that E _rev is more positive than the AP threshold. Thus activation of ionotropic receptors at excitatory synapses causes inward current to flow. This current drives V _m toward the AP threshold and is therefore depolarizing and excitatory.

The Reversal Potential of the EPC at the Frog NMJ.

The muscle V _m was voltage-clamped and an EPC was recorded in response to stimulation of the motor nerve. (A) EPCs recorded at membrane potentials between –120 mV and +38 mV. At negative V _m , the EPC is inward; at positive V _m , the EPC is outward. (B) The amplitude of the EPC is plotted as a function of V _m . The reversal potential ( E _rev ) of the EPC is close to 0 mV.

(Data from Nichols, J.G., Martin, A.R., & Wallace, B.G. From neuron to brain, ed 3, Sunderland, Mass, 1992, Sinauer.)

NMDAR and AMPAR are channels with different ion selectivities and kinetics

All ionotropic glutamate receptors are nonselective cation channels permeable to both Na ⁺ and K ⁺ , with E _rev ≈ 0 mV. Thus activation of ionotropic glutamate receptors induces an inward excitatory postsynaptic current (EPSC). In turn, the EPSC generates an excitatory postsynaptic potential (EPSP) , which depolarizes the cell toward the AP threshold.

NMDARs have additional properties that are functionally important. First, extracellular Mg ²⁺ blocks the NMDAR channel in a voltage-dependent manner ( Fig. 13.5 and Box 13.4 ). At negative V _m , Mg ²⁺ is driven into the channel and acts like a plug—it lodges in the pore and blocks current flow through the channel. At positive V _m , Mg ²⁺ is driven out of the channel and relieves the block ( Fig. 13.5 ). Thus the channel exhibits outward rectification : it conducts outward current better than inward current. A second important property of NMDAR channels is that they are also permeable to Ca ²⁺ . Ca ²⁺ entry through these channels can increase [Ca ²⁺ ] _i and activate Ca ²⁺ -dependent signaling cascades in the postsynaptic cell. Because Mg ²⁺ block of NMDAR channels is relieved by depolarization, current flow and thus Ca ²⁺ entry through NMDAR channels occur at depolarized V _m ( Fig. 13.5 ).

Mg ²⁺ Blocks NMDAR Channels.

(A) Macroscopic (whole-cell) currents in mouse brain neurons induced by glutamate are plotted as a function of V _m . In the absence of Mg ²⁺ ( circles ) the current-voltage relationship is approximately linear between +60 and –60 mV. After addition of 500 μM extracellular Mg ²⁺ ( squares ) , the currents are greatly reduced at negative potentials. At negative V _m , Mg ²⁺ is driven into the channel where it blocks current flow. (B) In the absence of Mg ²⁺ , glutamate induces relatively long-lasting single-channel openings at both +40 and –60 mV. In the presence of 10 μM Mg ²⁺ , the currents at +40 mV are unchanged, whereas at –60 mV, the single channel openings appear as rapid bursts. This is because Mg ²⁺ ions rapidly enter and exit the channel, which causes the channel to switch rapidly between blocked and unblocked states.

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Electrical consequences of ionic gradients Ion channels Active transport Synaptic physiology I Summary of elementary circuit theory Answers to study problems

Stay updated, free articles. Join our Telegram channel

Join