Smith R D, Goldin A L
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Am J Physiol. 1992 Sep;263(3 Pt 1):C660-6. doi: 10.1152/ajpcell.1992.263.3.C660.
The voltage-sensitive rat brain sodium channel is known to be phosphorylated by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA), but the functional significance of that phosphorylation is unknown. We have shown that rat brain sodium channel currents expressed in Xenopus oocytes were enhanced by induction of PKA activity. Stimulation of the beta 2-adrenergic receptor or treatment with dibutyryl cAMP resulted in increased sodium current amplitudes without affecting the voltage dependence of channel activation or inactivation. These increases were completely blocked by preinjection of protein kinase inhibitor, a specific inhibitor of PKA. Injection of phosphatase into the oocytes resulted in a significant decrease in sodium current amplitude, indicating that phosphorylation is important for basal levels of sodium channel activity in oocytes. The enhancement was specific for the rat brain IIA sodium channel, because currents expressed from the rat muscle microI sodium channel were not enhanced by the same procedures. These data demonstrate a modulatory role of PKA phosphorylation on brain sodium channel function and suggest a means by which the electrical excitability of cells may be regulated.
已知电压敏感的大鼠脑钠通道可被3',5'-环磷酸腺苷（cAMP）依赖性蛋白激酶A（PKA）磷酸化，但其磷酸化的功能意义尚不清楚。我们已经表明，非洲爪蟾卵母细胞中表达的大鼠脑钠通道电流可通过诱导PKA活性而增强。刺激β2-肾上腺素能受体或用二丁酰cAMP处理会导致钠电流幅度增加，而不影响通道激活或失活的电压依赖性。这些增加被预先注射蛋白激酶抑制剂（一种PKA的特异性抑制剂）完全阻断。向卵母细胞中注射磷酸酶会导致钠电流幅度显著降低，表明磷酸化对于卵母细胞中钠通道活性的基础水平很重要。这种增强对大鼠脑IIA钠通道具有特异性，因为通过相同程序，大鼠肌肉微小I钠通道表达的电流并未增强。这些数据证明了PKA磷酸化对脑钠通道功能的调节作用，并提示了一种调节细胞电兴奋性的方式。
