Wisgirda M E, Dryer S E
Department of Biological Science B-221, Florida State University, Tallahassee 32306-4075.
Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2858-62. doi: 10.1073/pnas.91.7.2858.
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.
钙离子内流控制着可兴奋细胞中的许多重要过程，包括对钙激活钾通道（电流IK[Ca]）门控的调节。各种IK[Ca]通道参与动作电位波形的调节、峰电位的重复发放以及神经递质的分泌。据认为，大电导IK[Ca]通道必须与钙通道（ICa）紧密共定位才能被钙离子内流门控。我们现在报告，IK[Ca]通道可以优先与药理学上不同亚型的电压激活钙通道共定位，并且这种情况在胚胎鸡交感神经元和副交感神经元中有所不同。通过对胚胎鸡睫状神经节和交感神经节神经元进行穿孔膜片全细胞记录，研究了各种二氢吡啶和ω-芋螺毒素对电压激活钙电流（ICa）和钙激活钾电流（IK[Ca]）的影响。应用硝苯地平或ω-芋螺毒素均可使ICa降低40%-60%，而应用S-(-)-BAY K 8644可增强睫状神经节神经元中的ICa。但是，应用ω-芋螺毒素对IK[Ca]几乎没有影响，而硝苯地平和S-(-)-BAY K 8644分别抑制和增强IK[Ca]。这些结果表明，IK[Ca]通道在鸡睫状神经节神经元上优先与L型而非N型钙通道偶联。鸡交感神经元也表达对二氢吡啶敏感和对ω-芋螺毒素敏感的ICa成分。然而，在这些细胞中，应用ω-芋螺毒素可使IK[Ca]降低40%-60%，而硝苯地平仅在部分细胞亚群中降低IK[Ca]。因此，交感神经元中的IK[Ca]要么与N型钙通道偶联，要么不选择性地与单一钙通道亚型偶联。IK[Ca]通道与不同ICa亚型的优先偶联可能是允许对神经递质释放进行选择性调节的机制的一部分。优先偶联对于脊椎动物神经元的分化和发育也可能很重要。
