Vasopressin modulates the spontaneous electrical activity in aortic cells (line A7r5) by acting on three different types of ionic channels.

Abstract

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.

Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4–8)

“…This and other effects of VP on brain neurons, such as reversible depolarization, increase in input resistance and spontaneous activity, and activation of a voltage-dependent inward current [38,43,47,51,75], could thus be a result of different intracellular effector pathways being activated by these peptides via the same or different membrane receptors. Activation of three different intracellular effector pathways by activation of the same VP receptor has been demonstrated [35,72]. Two neurons showed a peptide-induced increase in EPSPs while the first action potential was delayed and the threshold increased.…”

“…A decreased synaptic inhibition or increased Ca-" + influx through NMDA receptors is therefore unlikely to be the mechanism of the EPSP-potentiating action of the peptides. However, VP and VP(4-8) stimulate inositol phospholipid metabolism in neurons [44,54], mobilize Ca e+ from internal stores in cultured hippocampus neurons and in vascular smooth muscle cells [6,72], and increase transmitter release [1]. Thus, VP and VP(4-8) might have facilitated the EPSPs through a Ca2+-dependent mechanism, leading to an increase in glutamate release.…”

Ca2+ Selectivity and Fatty Acid Specificity of the Noncapacitative, Arachidonate-regulated Ca2+ (ARC) Channels

“…However, there is increasing evidence that receptor-activated Ca 2ϩ entry in A7r5 cells, and probably other smooth muscle cells, occurs via nonselective cation channels, rather than the highly Ca 2ϩ -selective channels (e.g. CRAC and/or ARC) seen in many other cell types (42)(43)(44). Our direct examination of Ca 2ϩ entry through the Ca 2ϩ -selective noncapacitative ARC channels clearly shows that 1 M Gd 3ϩ is capable of significantly inhibiting this entry, a fact supported by fluorescence measurements of arachidonic acid-induced increases in cytosolic Ca 2ϩ .…”

An inverse relationship between receptor internalization and the fraction of laterally mobile receptors for the vasopressin renal‐type V2‐receptor

“…This introduces the interesting possibility, not only that receptor lateral mobility plays a role in signal transduction by bringing proteins into contact with one Tables I and II another in the plasma membrane lipid bilayer, but that lateral diffusion of receptors may also be important in receptor down-regulation through endocytosis. The EGF- [15,21,22,25], insulin- [26,27] and Vl-receptor [13, [28][29][30]] systems all display not only rapid activation of signal transduction, but also rapid desensitization of response concomitant with very rapid receptor internalization. The V2-receptor shows both slower activation and down-regulation kinetics, concomitant with lower receptor lateral diffusion rates and slower receptor internalization kinetics.…”