Stimulation of L-type Ca2+ channels by inositol pentakis- and hexakisphosphates in rat vascular smooth muscle cells

The electrophysiological effects Of D-myo-inositol 1,3,4,5,6-pentakisphosphate (InsP,) and D-myoinositol hexakisphosphate (InsP(6)), which represent the main cellular inositol polyphosphates, were studied on L-type Ca2+ channels in single myocytes of rat portal vein. Intracellular infusion of InsP, (up to 50 mum) or 10 mum InsP(6) had no action on Ba2+ current, whereas 50 mum InsP(6) or 10 mum InsP(5) plus 10 mum InsP(6) (InSP5,6) stimulated the inward current. The stimulatory effect of InsP(5,6) was also obtained in external Ca2+-containing solution. The stimulated Ba2+ current retained the properties of L-type Ba2+ current and was oxodipine sensitive. PKC inhibitors Ro 32-0432 (up to 500 nm), GF109203X (5 mum) or calphostin C (100 nm) abolished the InSP5,6-induced stimulation. Neither the PKA inhibitor H89 (1 mum) nor the protein phosphatase inhibitors okadaic acid (500 nm) or cypermethrin (1 mum) prevented or mimicked the InSP5,6-induced stimulation of Ba2+ current. However, InsPs or InsP(6) could mimic some effects of protein phosphatase inhibitor so as to extend after washing-out forskolin the stimulatory effects of the adenylyl cyclase activator on Ba2+ current. These results indicate that InsP(5) and InsP(6) may act as intracellular messengers in modulating L-type Ca2+ channel activity and so could be implicated in mediator-induced contractions of vascular smooth muscle cells.