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Sensitivity limits for voltage control of P2Y receptor‐evoked Ca 2+ mobilization in the rat megakaryocyte
Author(s) -
MartinezPinna Juan,
Tolhurst Gwen,
Gurung Iman S.,
Vandenberg Jamie I.,
MahautSmith Martyn P.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.056846
Subject(s) - depolarization , biophysics , membrane potential , hyperpolarization (physics) , chemistry , receptor , electrophysiology , intracellular , resting potential , endocrinology , medicine , neuroscience , biology , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
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 Ca 2+ 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 Ca 2+ concentration ([Ca 2+ ] i ) in response to depolarization was always larger than the maximal reduction in [Ca 2+ ] i following an equivalent amplitude hyperpolarization. Significant [Ca 2+ ] 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 Ca 2+ release and the response to trains of normally paced stimuli fused to generate prolonged [Ca 2+ ] i increases. Furthermore, elevation of the temperature to physiological levels (36°C) resulted in a more sustained depolarization‐evoked Ca 2+ increase compared with more transient or oscillatory responses at 20–24°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.