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.
Martínez-Pinna
J
J
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Apartado 18, 03550 San Juan de Alicante, Spain.
McLachlan
E M
EM
Gallego
R
R
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018118:Chloride Channels; D015221:Potassium Channels; D020867:omega-Agatoxin IVA; D012433:Ryanodine; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D002118:Calcium