P2 receptor-mediated Ca2+ transients in rat cerebral artery smooth muscle cells

Open Access
Publisher Website
Google Scholar
Abstract
Significant Ca2+ release was previously noted with the activation of L-type Ca2+ current in rat superior cerebral artery smooth muscle cells. Here we examined whether the P2X current that is partly carried by Ca2+ also triggers Ca2+ release in this preparation. Application of P2X agonists evoked membrane currents and concomitant Ca2+ transients in whole cell voltage-clamped single cells. The expected increase in intracellular Ca2+ concentration ([Ca2+]i) was calculated from the time-integrated P2X current by assuming Ca2+ is the only charge carrier. The measured increase in [Ca2+]i was plotted as a function of the expected increase in [Ca2+]i, and Ca2+-buffering power was obtained as a reciprocal of the linear fit to this relationship. Both ryanodine, a Ca2+-induced Ca2+-release inhibitor, and cADP ribose, a putative activator of Ca2+-induced Ca2+ release, had no significant effects on Ca2+-buffering power. These results suggest that Ca2+ influx through P2X receptors does not trigger significant Ca2+ release. We then examined whether P2X responses influence the subsequent P2Y response. P2Y responses were characterized by measuring the rate of [Ca2+]i increase obtained as the slope of the linear regression to the rising phase of the Ca2+ transient. During simultaneous application of the P2X and P2Y agonist, the rate of [Ca2+]i increase was facilitated or suppressed depending on the size of the P2X receptor-mediated [Ca2+]i increase. Membrane depolarization close to the Ca2+ equilibrium potential significantly promoted the rate of [Ca2+]i increase. Our results suggest that the [Ca2+]i increase and membrane depolarization caused by the P2X current may regulate the subsequent P2Y response.