Mechanism of Inhibition in the Postsynaptic Membrane

We have seen repeatedly that changes in membrane potential are produced by changes in ionic permeability of the plasma membrane. The i.p.s.p. is no different in this regard. When the permeability of the membrane to a particular ion increases, the membrane potential tends to move toward the equilibrium potential for that ion. What change in permeability might result in a hyper-polarizing response like an i.p.s.p.? One possible answer is illustrated in Figure 9-8. If potassium permeability of a cell membrane increases, the membrane potential would be expected to move toward EK, which is about -85 mV for a typical mammalian cell (see Chapter 4). In this situation, pNa/pK would be smaller than usual, and the balance between potassium and sodium fluxes

Time

-100

Change in pk causes change in Em

Figure 9-8 The mechanism by which increasing potassium permeability produces an inhibitory postsynaptic potential in a postsynaptic neuron. (a) The membrane potential moves toward the potassium equilibrium potential (Ek) when potassium permeability (pK) increases. (b) At an inhibitory synapse, neurotransmitter molecules may act by opening potassium channels in the plasma membrane of a postsynaptic neuron. Efflux of potassium ions through the open channel then drives the membrane potential toward fK.

Inhibitory transmitter molecules Specific binding site ".' f Outside

Gate closed

Postsynaptic membrane

Gate closed

Transmitter binds to receptor site

Transmitter-activated K+ channel

Transmitter binds to receptor site

Transmitter-activated K+ channel

would be struck closer to EK. This is similar to the situation during the undershoot at the end of an action potential, when pNa/pK is transiently smaller than normal. As shown in Figure 9-8b, then, an inhibitory transmitter could hyper-polarize the postsynaptic cell by opening potassium channels in the postsyn-aptic membrane. As with ACh at the neuromuscular junction, the inhibitory transmitter might act by combining with specific binding sites associated with the gate on the channel. When the binding sites are occupied, the gate controlling movement through the channel opens, and potassium ions can move out of the cell, driving Em closer to the potassium equilibrium potential.

At many inhibitory synapses, however, the transmitter-activated post-synaptic channels are not potassium channels. Instead, inhibitory neuro-transmitters commonly open postsynaptic chloride channels, as illustrated schematically in Figure 9-9. In many neurons, chloride pumps in the plasma membrane maintain the chloride equilibrium potential, ECl, more negative than the resting membrane potential. An increase in chloride permeability will drive the membrane potential toward ECl and hyperpolarize the neuron. Thus, opening chloride channels can produce an i.p.s.p. in a postsynaptic cell.

In general, inhibition of a postsynaptic cell results when a neurotransmitter increases permeability to an ion whose equilibrium potential is more negative than the threshold potential for triggering an action potential. If the equilibrium potential for an ion is more negative than threshold, the ion will oppose any attempt to reach threshold as soon as the depolarization exceeds the ion's equilibrium potential. Thus, it is possible that inhibition could occur without any visible change in membrane potential from the resting level. For example, if the chloride equilibrium potential is equal to the resting potential, then opening a chloride channel would cause no change in membrane potential. However, if an excitatory input is activated, the size of the resulting e.p.s.p. would be reduced because of the enhanced ability of chloride ions to oppose depolarization.

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