title: Functional dependence of Ca(2+)-activated K+ current on L- and N-type Ca2+ channels: differences between chicken sympathetic and parasympathetic neurons suggest different regulatory mechanisms.
abstract: The influx of Ca2+ ions controls many important processes in excitable cells, including the regulation of the gating of Ca(2+)-activated K+ channels (the current IK[Ca]). Various IK[Ca] channels contribute to the regulation of the action-potential waveform, the repetitive discharge of spikes, and the secretion of neurotransmitters. It is thought that large-conductance IK[Ca] channels must be closely colocalized with Ca2+ channels (ICa) to be gated by Ca2+ influx. We now report that IK[Ca] channels can be preferentially colocalized with pharmacologically distinct subtypes of voltage-activated Ca2+ channel and that this occurs differently in embryonic chicken sympathetic and parasympathetic neurons. The effects of various dihydropyridines and omega-conotoxin on voltage-activated Ca2+ currents (ICa) and Ca(2+)-activated K+ currents (IK[Ca]) were examined by using perforated-patch whole-cell recordings from embryonic chicken ciliary and sympathetic ganglion neurons. Application of nifedipine or omega-conotoxin each caused a 40-60% reduction in ICa, whereas application of S-(-)-BAY K 8644 potentiated ICa in ciliary ganglion neurons. But application of omega-conotoxin had little or no effect on IK[Ca], whereas nifedipine and S-(-)-BAY K 8644 inhibited and potentiated IK[Ca], respectively. These results indicate that IK[Ca] channels are preferentially coupled to L-type, but not to N-type, Ca2+ channels on chicken ciliary ganglion neurons. Chicken sympathetic neurons also express dihydropyridine-sensitive and omega-conotoxin-sensitive components of ICa. However, in those cells, application of omega-conotoxin caused a 40-60% reduction in IK[Ca], whereas nifedipine reduced IK[Ca] but only in a subpopulation of cells. Therefore, IK[Ca] in sympathetic neurons is either coupled to N-type Ca2+ channels or is not selectively coupled to a single Ca(2+)-channel subtype. The preferential coupling of IK[Ca] channels with distinct ICa subtypes may be part of a mechanism to allow for selective modulation of neurotransmitter release. Preferential coupling may also be important for the differentiation and development of vertebrate neurons.
authors.affiliation: Department of Biological Science B-221, Florida State University, Tallahassee 32306-4075.
authors.forename: M E
authors.initials: ME
authors.lastname: Wisgirda
authors.forename: S E
authors.initials: SE
authors.lastname: Dryer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation; D002642:Chick Embryo; D004095:Dihydropyridines / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010455:Peptides; D015221:Potassium Channels; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D011188:Potassium; D002118:Calcium