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.
Quignard
J F
JF
Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017, UFR Sciences Pharmaceutiques, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France. jean-francois.quignard@umr5017.u-bordeaux2.fr
Rakotoarisoa
L
L
Mironneau
J
J
Mironneau
C
C
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002469:Cell Separation; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010833:Phytic Acid / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D020746:Calcium Channels, L-Type; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D047428:Protein Kinase Inhibitors; D005576:Colforsin; D019319:Okadaic Acid; C013571:inositol pentaphosphate; D010833:Phytic Acid; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases