Distinct mechanisms for activation of Cl- and K+ currents by Ca2+ from different sources in mouse sympathetic neurones.

We have investigated the roles of different voltage-dependent Ca2+ channels in the activation of the Cl- and K+ channels responsible for the afterdepolarization (ADP) and slow afterhyperpolarization (AHP) in sympathetic neurones of the isolated mouse superior cervical ganglion in vitro. The ADP and its associated Ca2+-activated Cl- current were markedly decreased by omega-agatoxin IVA (40-200 nM) and nifedipine (1-10 microM), but not by omega-conotoxin GVIA (300 nM). In contrast, the AHP and the apamin-sensitive Ca2+-activated K+ current that underlies this potential were blocked by omega-conotoxin GVIA, but were not affected by omega-agatoxin IVA and were only slightly reduced by nifedipine. Ryanodine (20 microM) reduced the Ca2+-activated Cl- current following an action potential by 75% but on average did not affect the Ca2+-activated K+ current. Evidence that R-type channels provide a proportion of the Ca2+ activating both types of Ca2+-dependent channel was obtained. We conclude that Ca2+ entering through L- and P-type Ca2+ channels preferentially activates the Cl- current responsible for the ADP in mouse sympathetic neurones, predominantly via Ca2+-induced Ca2+ release, whereas the Ca2+ that activates the K+ channels responsible for the AHP enters predominantly through N-type channels. The data can be explained by the selective association of each type of Ca2+ channel with particular intracellular mechanisms for activating other membrane channels, one indirect and the other direct, probably located at discrete sites on the soma and dendrites.