Vasopressin modulates the spontaneous electrical activity in aortic cells (line A7r5) by acting on three different types of ionic channels.
A7r5 smooth muscle (aorta) cells have a spontaneous electrical activity. Application of vasopressin produces a hyperpolarization accompanied by an interruption of the spontaneous activity, which is followed by a depolarization associated with a recovery of the spiking activity. Vasopressin action is produced by an action of the peptide on three different types of ionic channels. Vasopressin activates a Ca2+-sensitive K+ conductance, presumably by producing inositol 1,4,5-trisphosphate intracellularly and liberating Ca2+ from internal stores. This activation is transient (0.5-4 min) and is related to the vasopressin-induced hyperpolarization. Intracellular perfusion of inositol trisphosphate triggers by itself a transient K+ current and prevents subsequent activation by vasopressin. Vasopressin inhibits an L-type Ca2+ channel through both protein kinase C activation and a [Ca2+]i-dependent inactivation mechanism triggered by inositol trisphosphate production. The addition of the activation of a Ca2+-sensitive K+ channel and of the inhibition of a voltage-sensitive Ca2+ channel is responsible for the transient blockade of the spontaneous activity. Vasopressin also provokes the activation of an inward current (2-20 min) due to a nonselective channel able to transfer Ca2+, Na+, K+, and Cs+ across the membrane. This effect of the peptide is associated with the depolarization following the hyperpolarization phase.
Van Renterghem
C
C
Centre de Biochimie, Centre National de la Recherche Scientifique, Nice, France.
Romey
G
G
Lazdunski
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002414:Cations, Monovalent; D002460:Cell Line; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002414:Cations, Monovalent; D007473:Ion Channels; D001127:Arginine Vasopressin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013755:Tetradecanoylphorbol Acetate