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Ionotropic vs. metabotropic PSPs

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Presentation on theme: "Ionotropic vs. metabotropic PSPs"— Presentation transcript:

1 Ionotropic vs. metabotropic PSPs
Figure 5-1. Postsynaptic potentials (PSPs) mediated by ionotropic receptors, such as the AMPA receptor for glutamate and the GABAA receptor for GABA, reach their peak potentials rapidly and also return to baseline rapidly (A). In contrast to these fast postsynaptic potentials, slow postsynaptic potentials mediated by metabotropic receptors, such as the GABAB receptor, have a delayed onset and can last for hundreds of milliseconds or even seconds or minutes (B). When a ligand binds to a metabotropic receptor, a series of intracellular reactions may eventually result in the opening or closing of ion channels and consequently a change in membrane potential. The magnitude of postsynaptic potentials, mediated by either receptor type, varies widely and only representative examples are shown here. The time course of metabotropic receptor-mediated postsynaptic potentials also varies a great deal; relatively short metabotropic receptor-mediated postsynaptic potentials are illustrated here.

2 The length constant Figure 5-2. The length constant is a measure of how far a potential travels along a cylinder before decaying to 37% of its original peak amplitude. A: One length constant from its origin, an EPSP of initial magnitude 1.00 has a peak magnitude of B-D: By using a plumbing analogy, one can clearly see that either a leaky (low rm, B) or narrow (high ra, C) pipe results in a short length constant, whereas the opposite characteristics (high rm and low ra, D) result in a long length constant.

3 The time constant Figure 5-3. The time constant, τ, is the time needed for the membrane potential to reach 63% of its peak value. Consider two cells that differ only in their relative time constants. These cells receive the same synaptic input (inset at top). Cell 1 has a short time constant (solid line below trace), and its synaptic response reaches 63% of its maximal value after a shorter time (A) than does the synaptic response of cell 2 with a longer time constant (B). Furthermore, if a second input (hollow arrowhead) occurs shortly after the first input (filled arrowhead), then temporal summation (dashed lines in A–B) will only occur in cell 2, the cell with the long time constant. Cell 1, which has a short time constant, has the same response to both inputs. Thus, cells with longer time constants can summate inputs over a longer period of time.

4 The action potential Figure 5-4. During an action potential, the membrane potential shoots up from rest, anywhere from -70 mV to -50 mV, to a positive value before returning to rest. An undershoot or afterhyperpolarization occurs as the membrane potential initially repolarizes beyond the rest potential before eventually, and relatively slowly, returning to rest. The entire action potential occurs in one to a few milliseconds, with the rising phase occurring in under a millisecond.

5 Voltage-gated sodium channels
Figure 5-5A: Voltage-gated sodium channels (VGSCs) change conformation from the closed (C) to the open (O) state when the membrane potential depolarizes above rest. Immediately after opening, VGSCs enter an inactivated (I) state. The transition from the open to the inactivated state is automatic and cannot be bypassed. To recover from inactivation and reenter the closed state, the membrane potential must hyperpolarize to near rest potential.

6 Relative refractory period
Figure 5-5B: The rapid opening of VGSCs (CO) is responsible for the rising phase of the action potential. Yet, VGSCs enter the inactivated state immediately after opening (COI), rendering the membrane unexcitable because the inactivated VGSCs cannot open. During the decay phase of the action potential, most of the VGSCs are inactivated and there are not enough closed VGSCs to support an action potential; this period is the absolute refractory period. As the membrane potential approaches the rest potential, more and more VGSCs transition from inactivated to closed (IC), a period that is termed the relative refractory period.

7 Absolute refractory period
Figure 5-5C: If a cell depolarizes slowly, over seconds to minutes, VGSCs open and become inactivated just as they do when a cell depolarizes quickly over a few milliseconds. However, in the case of a slow depolarization, no action potential can occur because not enough VGSCs are closed and available for opening once threshold is reached. Therefore, a slow depolarization leads to a persistent state of absolute refractoriness.

8 Recovery of action potential
Figure 5-5D: When a cell repolarizes from an action potential to near the rest potential, the relative refractory period starts. During the relative refractory period, action potentials can occur. However, the depolarization needed to trigger an action potential (stimulus threshold) is greater than normal and the action potential peak (AP magnitude) is lower. After more and more time at a hyperpolarized potential, more and more VGSCs recover from inactivation, and consequently, the action potential returns to normal.

9 Myelination and AP conduction
Figure 5-6A: At axonal nodes, no myelin is present and VGSCs that are packed at high density support sodium ion influx during action potentials. In the paranode, the myelin wraps begin. The myelin wrapping around myelinated axons is restricted to the internodes. B: Action potentials move along a myelinated axon by saltatory conduction, meaning that the action potential jumps from one node to the next without depolarizing the internodes. In this example, the action potential is moving from left (1) to right (4). C: At any one moment, action potentials occur in multiple nodes (four are illustrated) as the rising phase of an action potential in one node leads to the depolarization of the next node, which then fires an action potential, which in turn depolarizes the subsequent node and so on. Action potentials are numbered for the node from which they arise, as labeled in B.

10 Neuronal polarization
Axons are not polarized. Consequently an action potential initiated at B will travel towards both C and A. However, because of sodium channel inactivation, an action potential arriving at B from C cannot travel back to C and will continue only in the direction of A.


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