title: Sensitivity limits for voltage control of P2Y receptor-evoked Ca2+ mobilization in the rat megakaryocyte.
abstract: G-protein-coupled receptor signalling has been suggested to be voltage dependent in a number of cell types; however, the limits of sensitivity of this potentially important phenomenon are unknown. Using the non-excitable rat megakaryocyte as a model system, we now show that P2Y receptor-evoked Ca2+ mobilization is controlled by membrane voltage in a graded and bipolar manner without evidence for a discrete threshold potential. Throughout the range of potentials studied, the peak increase in intracellular Ca2+ concentration ([Ca2+]i) in response to depolarization was always larger than the maximal reduction in [Ca2+]i following an equivalent amplitude hyperpolarization. Significant [Ca2+]i increases were observed in response to small amplitude (< 5 mV, 5 s duration) or short duration (25 ms, 135 mV) depolarizations. Individual cardiac action potential waveforms were also able to repeatedly potentiate P2Y receptor-evoked Ca2+ release and the response to trains of normally paced stimuli fused to generate prolonged [Ca2+]i increases. Furthermore, elevation of the temperature to physiological levels (36 degrees C) resulted in a more sustained depolarization-evoked Ca2+ increase compared with more transient or oscillatory responses at 20-24 degrees C. The ability of signalling via a G-protein-coupled receptor to be potentiated by action potential waveforms and small amplitude depolarizations has broad implications in excitable and non-excitable tissues.
authors.affiliation: Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Martinez-Pinna
authors.forename: Gwen
authors.initials: G
authors.lastname: Tolhurst
authors.forename: Iman S
authors.initials: IS
authors.lastname: Gurung
authors.forename: Jamie I
authors.initials: JI
authors.lastname: Vandenberg
authors.forename: Martyn P
authors.initials: MP
authors.lastname: Mahaut-Smith
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D008297:Male; D008533:Megakaryocytes / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012680:Sensitivity and Specificity
chemical_list: D018048:Receptors, Purinergic P2