The Journal of Neurophysiology Vol. 84 No. 3 September 2000, pp. 1346-1354
Copyright ©2000 by the American Physiological Society

Diversity of Channels Involved in Ca²⁺ Activation of K⁺ Channels During the Prolonged AHP in Guinea-Pig Sympathetic Neurons

 ¹Prince of Wales Medical Research Institute (affiliated with the University of New South Wales), Randwick, Sydney, NSW 2031, Australia; and  ²Instituto de Neurociencias, Universidad Miguel Hernández, 03550 Alicante, Spain

Martínez-Pinna, Juan, Philip J. Davies, and Elspeth M. McLachlan. Diversity of Channels Involved in Ca²⁺ Activation of K⁺ Channels During the Prolonged AHP in Guinea-Pig Sympathetic Neurons. J. Neurophysiol. 84: 1346-1354, 2000. 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 -conotoxin GVIA) and P-type Ca²⁺ channels (with 40 nM -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.