Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells.

Abstract

Healthy bullfrog sympathetic ganglion cells often show a two-component afterhyperpolarization (AHP). Both components can be reduced or abolished by adding Cachannel blockers or by removing external Ca. Application of a single electrode "hybrid clamp"-i.e., switching from current-to voltage-clamp at the peak of the AHP, reveals that the slow AHP component is generated by a small, slow, monotonically decaying outward current, which we call Ihm. IAHP is blocked by Ca-removal or by apamin and is a pure K current. It is slightly sensitive to muscarine and to tetraethylammonium ion but is much less so than muscarine-sensitive (IM) and fast Ca-dependent (Ic) K currents. It also can be recorded in dualelectrode voltage-clamp experiments, where it is seen as a slow, small component of the outward tail current that follows brief depolarizations to 0 mV or beyond. Ic is seen as an early, fast, large component of the same tail current. Both components are blocked by Ca removal, but only the Ic component is blocked by low doses of tetraethylammonium ion. Thus, bullfrog ganglion cells exhibit two quite distinct Ca-dependent K currents, which differ in size, voltage-sensitivity, kinetics, and pharmacology. These two currents also play quite separate roles in shaping the action potential.Recent voltage-clamp work in bullfrog sympathetic ganglion cells (1-3) has established the existence of a large, rapid Caactivated K current that is partly responsible for spike repolarization and early afterhyperpolarization (AHP). This current, which we term Ic, has several hallmarks: sensitivity to tetraethylammonium ion (Et4N+); insensitivity to muscarine, apamin, and barium; and a strong voltage dependence.It is carried by high-conductance channels like those in chromaffin cells and myotubes (4, 5). However, carefully impaled bullfrog neurons often show a second slow component of the afterhyperpolarization, which, while dependent on Ca-influx, seems to be inhibited by muscarinic-receptor activation (6) and rather insensitive to membrane potential (7). We have investigated this slow AHP component using voltage-clamp techniques, and we find that it is due to a Cadependent K current that, while it has some similarities to both Ic and the muscarine-sensitive K current, which we call IM (8)

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

“…This apparent absence of the apamin-sensitive, low conductance, CaZ+-activated K + channel accords with the ineffectiveness of apamin in the mammalian hippocampus [14,18], as distinct from the PNS of both amphibians and mammals [16,17].…”

“…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]. By analogy, the slow after-hyperpolarization in the CNS may also be mediated by such low conductance channels although no apamin sensitivity has yet been reported therein ( [14,18]; but see [19]).…”

Molecular Identification and Functional Roles of a Ca2+-activated K+ Channel in Human and Mouse Hearts

“…Physiological Significance-SK channels have been shown to play an important role in setting the tonic firing frequency of neurons (33). Their activation causes membrane hyperpolarization, which inhibits cell firing and limits the firing frequency of repetitive APs.…”

Regional Differences in Distribution and Functional Expression of Small-Conductance Ca2+-Activated K+Channels in Rat Brain

“…To compare the Ca 2ϩ -activated K ϩ currents (AHP currents; Pennefather et al, 1985;Lancaster and Adams, 1986;Storm, 1990;Stocker et al, 1999) in the three cell populations, each cell was voltage-clamped at a holding potential of Ϫ50 or Ϫ55 mV. One micromolar TTX and 5 mM TEA were routinely added to the extracellular medium to record the SK currents in relative isolation (see Materials and Methods).…”