Role of intracellular calcium in fast and slow desensitization of P2-receptors in PC12 cells

Br J Pharmacol. 1997 Apr;120(8):1552-60. doi: 10.1038/sj.bjp.0701060.


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 P2-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 linearly dependent on holding membrane potential, suggesting that Ca2+ influx is the predominant cause of [Ca2+]i elevation. This view was supported by experiments carried out in Ca(2+)-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 P2-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 P2-receptors, thus proposing this divalent cation as an intracellular factor able to provide an efficient and reversible control over receptor activity induced by ATP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcium / metabolism*
  • Kinetics
  • PC12 Cells
  • Patch-Clamp Techniques
  • Rats
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism*


  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Calcium