[Modulation of the voltage-dependent Ca2+ channels of smooth muscle by phosphorylation].
The voltage-dependent Ca2+ channels (VDC) in smooth muscle cell membranes are the major pathway by which Ca2+ enters the cell during contraction. It has been reported that VDC can be modulated by reversible channel protein phosphorylation and dephosphorylation reactions. In intestinal smooth muscle cell, muscarinic agents have been reported to increase the break-down of phosphatidylinositol 4,5-bisphosphate, which indicates that inositol-1,4,5-trisphosphate and diacylglycerol (DG) can be generated. DG activates protein kinase C. Carbachol (CCh), phorbol 12,13-dibutyrate and phosphatase inhibitors, okadaic acid and calyculin A increased the inward currents passing through the L-type VDCs. These effects were inhibited by protein kinase inhibitors, H-7 and staurosporine. The CCh effect was also inhibited by GDP beta S. Therefore, it seems possible that DG, a product of phosphatidylinositol break-down might mediate muscarinic effects on L-type VDC, the last via stimulation of protein kinase C, and that L-type VDC activity might be modulated by protein kinase C-mediated phosphorylation and protein phosphatase type-1-mediated dephosphorylation of the channel or related protein(s) in guinea pig taenia coli smooth muscle cells.
Department of Physiology, Sapporo Medical College, Hokkaido, Japan.
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Obara
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Yabu
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D011506:Proteins; D002217:Carbachol; D010741:Phospholipases A; D010744:Phosphoric Monoester Hydrolases; D010738:Type C Phospholipases