Modulation of L-type calcium channels by sodium ions.

It is universally believed that the removal of external sodium ions is without effect on calcium current. We now report that in enzymatically isolated guinea pig ventricular cells, the replacement of external sodium ions with certain other cations causes a 3- to 6-fold increase in peak L-type calcium current. The increase in current is reversibly blocked by L-type calcium-channel antagonists, not mediated by changes in internal calcium, and is inhibited by intracellular 5'-adenylyl imidodiphosphate, a nonhydrolyzable ATP analogue. The effects of sodium removal (and isoproterenol) were almost completely blocked by intracellular application of a specific (peptide) inhibitor of cAMP-dependent protein kinase. These experiments demonstrate a previously unknown effect of sodium ions to modulate calcium-channel phosphorylation via cAMP-dependent protein kinase.

学界普遍认为，移除细胞外钠离子不会对钙电流产生影响。本研究在经酶解法分离的豚鼠心室肌细胞中发现，用特定阳离子替换细胞外钠离子后，L型钙电流的峰值可升高3至6倍。该电流增幅可被L型钙通道拮抗剂可逆阻断，且并非由细胞内钙浓度变化所介导，同时会被细胞内的5'-腺苷酰亚胺二磷酸（5'-adenylyl imidodiphosphate）——一种非水解型ATP类似物——所抑制。移除钠离子（以及异丙肾上腺素）所引发的效应，几乎可被通过胞内给药方式施加的环腺苷酸依赖性蛋白激酶（cAMP-dependent protein kinase）特异性肽类抑制剂完全阻断。本实验揭示了钠离子此前未被报道的调控作用：通过环腺苷酸依赖性蛋白激酶调节钙通道的磷酸化过程。