FUNCTIONAL DEPENDENCE OF CA2+-ACTIVATED K+ CURRENT ON L-TYPE AND N-TYPE CA2+ CHANNELS - DIFFERENCES BETWEEN CHICKEN SYMPATHETIC AND PARASYMPATHETIC NEURONS SUGGEST DIFFERENT REGULATORY MECHANISMS

The influx of Ca2+ ions controls many important processes in excitable cells, including the regulation of the gating of Ca2+-activated K+ channels (the current I(K[Ca])). Various I(K[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 I(K[Ca]) channels must be closely colocalized with Ca2+ channels (I(Ca)) to be gated by Ca2+ influx. We now report that I(K[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 (I(Ca)) and Ca2+-activated K+ currents (I(K[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 I(Ca), whereas application of S-(-)-BAY K 8644 potentiated I(Ca) in ciliary ganglion neurons. But application of omega-conotoxin had little or no effect on I(K[Ca]), whereas nifedipine and S-(-)-BAY K 8644 inhibited and potentiated I(K[Ca]), respectively. These results indicate that I(K[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 dihyropyridine-sensitive and omega-conotoxin-sensitive components of I(Ca). However, in those cells, application of omega-conotoxin caused a 40-60% reduction in I(K[Ca]), whereas nifedipine reduced I(K[Ca]) but only in a subpopulation of cells. Therefore, I(K[Ca]) in sympathetic neurons is either coupled to N-type Ca2+ channels or is not selectively coupled to a single Ca2+-channel subtype. The preferential coupling Of I(K[Ca]) channels with distinct I(Ca) 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.