1 Combined whole-cell patch clamp recording and confocal laser scanning microscopy of [Ca2+](i) transients were performed on single PC12 cells to study any correlation between membrane currents induced by ATP and elevation in [Ca2+](i). ATP was applied by pressure from micropipettes near the recorded PC12 cells continuously superfused at a fast rate, 2 Brief (20 ms) pulses of ATP elicited monophasic inward currents and [Ca2+](i) increases. Long applications (2 s) of ATP (5 mM) evoked peak currents which rapidly faded during the pulse and were followed by a large rebound current, interpreted as due to rapid desensitization and recovery of P-2-receptors. The associated [Ca2+](i) increase grew monotonically to a peak reached only after the occurrence of the current rebound, indicating that it is unlikely this cation has a role in fast desensitization. 3 Both membrane currents and [Ca2+](i) transients were dependent on holding membrane potential, suggesting that Ca2+ influx is the predominant cause of [Ca2+](i) elevation. Tills view was supported by experiments carried out in Ca2+-free solution. 4 Brief pulses of ATP applied after a desensitizing pulse (2 s) of the same elicited smaller inward currents and [Ca2+](i) rises indicating a role for [Ca2+](i) in controlling slow desensitization of P-2-receptors. 5 This notion was confirmed in experiments with various [Ca2+](i) chelators which differentially affected slow desensitization in relation to their buffering capacity, while sparing fast receptor desensitization, 6 These results suggest a role for [Ca2+](i) in slow rather than fast desensitization of P-2-receptors, thus proposing this divalent cation as an intracellular factor able to provide an efficient and reversible control over receptor activity induced by ATP.
Role of intracellular calcium in fast and slow desensitization of P2-receptors in PC12 cells / Khiroug, L; Giniatullin, R; Talantova, M; Nistri, Andrea. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 120:8(1997), pp. 1552-1560. [10.1038/sj.bjp.0701060]
Role of intracellular calcium in fast and slow desensitization of P2-receptors in PC12 cells
Nistri, Andrea
1997-01-01
Abstract
1 Combined whole-cell patch clamp recording and confocal laser scanning microscopy of [Ca2+](i) transients were performed on single PC12 cells to study any correlation between membrane currents induced by ATP and elevation in [Ca2+](i). ATP was applied by pressure from micropipettes near the recorded PC12 cells continuously superfused at a fast rate, 2 Brief (20 ms) pulses of ATP elicited monophasic inward currents and [Ca2+](i) increases. Long applications (2 s) of ATP (5 mM) evoked peak currents which rapidly faded during the pulse and were followed by a large rebound current, interpreted as due to rapid desensitization and recovery of P-2-receptors. The associated [Ca2+](i) increase grew monotonically to a peak reached only after the occurrence of the current rebound, indicating that it is unlikely this cation has a role in fast desensitization. 3 Both membrane currents and [Ca2+](i) transients were dependent on holding membrane potential, suggesting that Ca2+ influx is the predominant cause of [Ca2+](i) elevation. Tills view was supported by experiments carried out in Ca2+-free solution. 4 Brief pulses of ATP applied after a desensitizing pulse (2 s) of the same elicited smaller inward currents and [Ca2+](i) rises indicating a role for [Ca2+](i) in controlling slow desensitization of P-2-receptors. 5 This notion was confirmed in experiments with various [Ca2+](i) chelators which differentially affected slow desensitization in relation to their buffering capacity, while sparing fast receptor desensitization, 6 These results suggest a role for [Ca2+](i) in slow rather than fast desensitization of P-2-receptors, thus proposing this divalent cation as an intracellular factor able to provide an efficient and reversible control over receptor activity induced by ATP.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.