Diversity of channels involved in Ca2+ activation of K+ channels during the prolonged AHP in guinea-pig sympathetic neurons

The types of Ca2+-dependent K+ channel involved in the prolonged afterhyperpolarization (AHP) in a subgroup of sympathetic neurons have been investigated in guinea pig celiac ganglia in vitro. The conductance underlying the prolonged AHP (gKCa2) was reduced to a variable extent in 100 nM apamin, an antagonist of SK-type Ca2+-dependent K+ channels, and by about 55% in 20 nM iberiotoxin, an antagonist of BK-type Ca2+-dependent K+ channels. The reductions in gKCa2 amplitude by apamin and iberiotoxin were not additive, and a resistant component with an amplitude of nearly 50% of control remained. These data imply that, as well as apamin- and iberiotoxin-sensitive channels, other unknown Ca2+-dependent K+ channels participate in gKCa2. The resistant component of gKCa2 was not abolished by 0.5-10 mM tetraethylammonium, 1 mM 4-aminopyridine, or 5 mM glibenclamide. We also investigated which voltage-gated channels admitted Ca2+ for the generation of gKCa2. Blockade of Ca2+ entry through L-type Ca2+ channels has previously been shown to reduce gKCa2 by about 40%. Blockade of N-type Ca2+ channels (with 100 nM omega-conotoxin GVIA) and P-type Ca2+ channels (with 40 nM omega-agatoxin IVA) each reduced the amplitude of gKCa2 by about 35%. Thus Ca2+ influx through multiple types of voltage-gated Ca2+ channel can activate the intracellular mechanisms that generate gKCa2. The slow time course of gKCa2 may be explained if activation of multiple K+ channels results from Ca2+ influx triggering a kinetically invariant release of Ca2+ from intracellular stores located close to the membrane.