Chapter 12 Potassium currents in hippocampal pyramidal cells

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The hippocampal pyramidal cells provide an example of how multiple potassium (K) currents co-exist and function in central mammalian neurones. The data come from CA1 and CA3 neurones in hippocampal slices, cell cultures and acutely dissociated cells from rats and guinea-pigs. Six voltage- or calcium(Ca)-dependent K currents have so far been described in CA1 pyramidal cells in slices. Four of them (IA, ID, IK, IM) are activated by depolarization alone; the two others (IC, IAHP) are activated by voltage-dependent influx of Ca ions (IC may be both Ca- and voltage-gated). In addition, a transient Ca-dependent K current (ICT) has been described in certain preparations, but it is not yet clear whether it is distinct from IC and IA. (1) IA activates fast (within 10 ms) and inactivates rapidly (time constant typically 15–50 ms) at potentials positive to -60 mV; it probably contributes to early spike-repolarization, it can delay the first spike for about 0.1 s, and may regulate repetitive firing. (2) ID activates within about 20 ms but inactivates slowly (seconds) below the spike threshold (-90 to -60 mV), causing a long delay (0.5–5 s) in the onset of firing. Due to its slow recovery from inactivation (seconds), separate depolarizing inputs can be “integrated”. ID probably also participates in spike repolarization. (3) IK activates slowly (time constant, PROGRESS IN BRAIN RESEARCH, 20–60 ms) in response to depolarizations positive to -40 mV and inactivates (PROGRESS IN BRAIN RESEARCH about 5s) at -80 to -40 mV; it probably participates in spike repolarization. (4) IM activates slowly (PROGRESS IN BRAIN RESEARCH about 50 ms) positive to -60 mV and does not inactivate; it tends to attenuate excitatory inputs, it reduces the firing rate during maintained depolarization (adaptation) and contributes to the medium after-hyperpolarization (mAHP); IM is suppressed by acetylcholine (via muscarinic receptors), but may be enhanced by somatostatin. (5) IC is activated by influx of Ca ions during the action potential and is thought to cause the final spike repolarization and the fast AHP (although ICT may be involved). Like IM, it also contributes to the medium AHP and early adaptation. It differs from IAHP by being sensitive to tetraethylammonium (TEA, 1 mM), but insensitive to noradrenaline and muscarine. Large-conductance (BK; about 200 pS) Ca-activated K channels, which may mediate IC, have been recorded. (6) IAHP is slowly activated by Ca-influx during action potentials, causing spike-frequency adaptation and the slow AHP. Thus, IAHP exerts a strong negative feedback control of discharge activity. It is suppressed by noradrenaline via cyclic AMP, muscarinic agonists, serotonin, histamine, corticotropin-releasing factor and phorbol esters (activators of protein kinase C), and it is enhanced by adenosine. In addition to the above K currents, there are resting K currents, and receptor-operated K currents which contribute to the effects of acetylcholine, noradrenaline, serotonin, GABA, adenosine. In conclusion, a variety of different voltage-dependent K currents co-exist in these cells, apparently contributing specifically to various aspects of the cell's electrical properties, such as the resting potential (IK,rest), spike repolarization (IA, ID, IK, IC, ICT ?), spike-frequency adaptation and after-hyperpolarizations (IAHP, IM, IC), delayed excitation, slow repetitive firing and temporal integration (IA, ID); – and in mediating the effects of transmitter substances such as acetylcholine (IAHP, IM, IA), noradrenaline, histamine, serotonin, adenosine, corticotropin-releasing factor (IAHP) and somatostatin (IM). These multiple roles may help to explain why the cells are equipped with so many channel types.

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