Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
Cardiac Na+,Ca2+ exchange is activated by a mechanism that requires hydrolysis of adenosine triphosphate (ATP) but is not mediated by protein kinases. In giant cardiac membrane patches, ATP acted to generate phosphatidylinositol-4,5-bisphosphate (PIP2) from phosphatidylinositol (PI). The action of ATP was abolished by a PI-specific phospholipase C (PLC) and recovered after addition of exogenous PI; it was reversed by a PIP2-specific PLC; and it was mimicked by exogenous PIP2. High concentrations of free Ca2+ (5 to 20 microM) accelerated reversal of the ATP effect, and PLC activity in myocyte membranes was activated with a similar Ca2+ dependence. Aluminum reversed the ATP effect by binding with high affinity to PIP2. ATP-inhibited potassium channels (KATP) were also sensitive to PIP2, whereas Na+,K+ pumps and Na+ channels were not. Thus, PIP2 may be an important regulator of both ion transporters and channels.
Hilgemann
D W
DW
Department of Physiology, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75235-9040, USA.
Ball
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000535:Aluminum / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D006168:Guinea Pigs; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism* / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D010738:Type C Phospholipases / Q000378:metabolism
D002352:Carrier Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D000255:Adenosine Triphosphate; D012964:Sodium; D000535:Aluminum; D010738:Type C Phospholipases; D002118:Calcium