Open AccessFunctional 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.
Author(s) -
Mary E. Wisgirda,
Stuart E. Dryer
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.7.2858
Subject(s) - nifedipine , ciliary ganglion , voltage dependent calcium channel , chemistry , channel blocker , sympathetic ganglion , biophysics , reversal potential , dihydropyridine , voltage gated ion channel , medicine , endocrinology , electrophysiology , patch clamp , neuroscience , ion channel , biology , calcium , receptor , biochemistry
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.