Pharmacological and physiological properties of the after‐hyperpolarization current of bullfrog ganglion neurones.

Abstract

SUMMARY1. The slowly decaying, calcium-dependent after-hyperpolarization (a.h.p.) that follows action potentials in bullfrog ganglion B cells has previously been shown to be generated by a potassium current called IAHP. We have recorded IAHP using a switched, single-electrode hybrid clamp where current-clamp mode was changed to voltage-clamp mode immediately after repolarization of a spike or the last spike of a train.2. Reduction of extracellular calcium reduced the decay time Of IAHP following a single spike. At all levels of extracellular calcium tested (0 5-4 mM), the decay time of IAHP was longer following a train of action potentials than following a single action potential. Thus, the time course of IAHP evoked by action potentials is a function of the calcium load induced by the action potentials. Conversely, agents that reduce the amount of IAHP activated without affecting its rate of decay, probably do not affect calcium influx.3. Muscarine (2 or 10 #/M) inhibits IAHP following an action potential by at most 30 % and has no effect on decay rate Of IAHP. These results suggest that muscarine has little or no effect on either calcium influx or sequestration. Decay of the a.h.p. is accelerated by muscarine but this effect is due to an increased leak conductance.4. Charybdotoxin (CTX) between 4 and 20 nm, prolongs action potential duration in a manner consistent with blockade of the voltage-and calcium-dependent potassium current (Ic) involved in spike repolarization in these cells. This action is consistent with its reported action on analogous channels in other systems. However, CTX also reduces IAHP. Thus, in bullfrog ganglion neurones, two distinct calciumdependent potassium currents exhibit a comparable sensitivity to CTX. This cannot .be due to a decreased influx of calcium because the decay rate Of IAHP following an action potential is unchanged. The action of CTX was observed with both crude and purified preparations of CTX.

A Spontaneous Mutation InvolvingKcnq2(Kv7.2) Reduces M-Current Density and Spike Frequency Adaptation in Mouse CA1 Neurons

“…This result is consistent with the hypothesis that proper I K(M) function is an important component of normal SFA (Goh and Pennefather, 1987;Aiken et al, 1995). Another group, however, has shown that LPD does not affect SFA in cultured mouse and rat superior cervical ganglion neurons (Romero et al, 2004), although neurons of this population are not implicated in epilepsy.…”

“…Functional consequences of reduced I K(M) in spike frequency adaptation I K(M) activation regulates action potential generation and facilitates SFA; in response to membrane depolarization, I K(M) repolarizes neurons and decreases input resistance, which attenuates action potential frequency (Goh and Pennefather, 1987;Yue and Yaari, 2004). To test whether the decreased I K(M) density observed in Szt1 slices causes any observable changes in neuronal excitability, we monitored SFA in CA1 neurons in response to prolonged depolarization steps.…”

Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvβ1.1 A-type K + channels

“…It has been suggested that current underlying fAHP is through Ca 2ϩ -activated BK (Maxi K)-type K ϩ channels because of their blockade by low concentrations of tetraethylammonium, iberiotoxin, and paxilline (26)(27)(28), although exact identity of these channels has not been determined. mAHP is also activated rapidly after an action potential but decays with a time course of 50 to several hundred milliseconds (29,30).…”

Dendrotoxin and charybdotoxin increase the cytosolic concentration of free Ca2+ in cerebrocortical synaptosomes: An effect not shared by apamin

“…Charybdotoxin has been identified as a blocker of the large and intermediate conductance, Ca2+-sensitive, voltage-activated K ÷ channels from skeletal muscle [8,9] and the mammalian central nervous system (CNS) [10,11]; these channels have been implicated in repolarization following an action potential in both the amphibian peripheral nervous system (PNS) [13] and mammalian CNS [14,15]. Apamin inhibits the small conductance, Ca2+-dependent, voltage-insensitive K + channel [12] which appears to underlie the slow afterhyperpolarization that controls repetitive firing in the PNS [16,17].…”