P2 receptor-mediated Ca2+ transients in rat cerebral artery smooth muscle cells.
Significant Ca(2+) release was previously noted with the activation of L-type Ca(2+) current in rat superior cerebral artery smooth muscle cells. Here we examined whether the P(2X) current that is partly carried by Ca(2+) also triggers Ca(2+) release in this preparation. Application of P(2X) agonists evoked membrane currents and concomitant Ca(2+) transients in whole cell voltage-clamped single cells. The expected increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) was calculated from the time-integrated P(2X) current by assuming Ca(2+) is the only charge carrier. The measured increase in [Ca(2+)](i) was plotted as a function of the expected increase in [Ca(2+)](i), and Ca(2+)-buffering power was obtained as a reciprocal of the linear fit to this relationship. Both ryanodine, a Ca(2+)-induced Ca(2+)-release inhibitor, and cADP ribose, a putative activator of Ca(2+)-induced Ca(2+) release, had no significant effects on Ca(2+)-buffering power. These results suggest that Ca(2+) influx through P(2X) receptors does not trigger significant Ca(2+) release. We then examined whether P(2X) responses influence the subsequent P(2Y) response. P(2Y) responses were characterized by measuring the rate of [Ca(2+)](i) increase obtained as the slope of the linear regression to the rising phase of the Ca(2+) transient. During simultaneous application of the P(2X) and P(2Y) agonist, the rate of [Ca(2+)](i) increase was facilitated or suppressed depending on the size of the P(2X) receptor-mediated [Ca(2+)](i) increase. Membrane depolarization close to the Ca(2+) equilibrium potential significantly promoted the rate of [Ca(2+)](i) increase. Our results suggest that the [Ca(2+)](i) increase and membrane depolarization caused by the P(2X) current may regulate the subsequent P(2Y) response.
Kamishima
Tomoko
T
Department of Human Anatomy and Cell Biology, University of Liverpool, United Kingdom. kamishi@liv.ac.uk
Quayle
John M
JM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology
D018048:Receptors, Purinergic P2; D012433:Ryanodine; D002110:Caffeine; D000255:Adenosine Triphosphate; D002118:Calcium