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 (InsP5) and D-myo-inositol hexakisphosphate (InsP6), which represent the main cellular inositol polyphosphates, were studied on L-type Ca2+ channels in single myocytes of rat portal vein. Intracellular infusion of InsP5 (up to 50 micro M) or 10 micro M InsP6 had no action on Ba2+ current, whereas 50 micro M InsP6 or 10 micro M InsP5 plus 10 micro M InsP6 (InsP5,6) stimulated the inward current. The stimulatory effect of InsP5,6 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 micro M) or calphostin C (100 nM) abolished the InsP5,6-induced stimulation. Neither the PKA inhibitor H89 (1 micro M) nor the protein phosphatase inhibitors okadaic acid (500 nM) or cypermethrin (1 micro M) prevented or mimicked the InsP5,6-induced stimulation of Ba2+ current. However, InsP5 or InsP6 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 InsP5 and InsP6 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.