Phosphatidylinositol-4,5-bisphosphate (PIP2) generated by ATP hydrolysis regulates cardiac Na+,Ca2+ exchange and ATP-inhibited potassium channels, but not Na+,K+ pumps or Na+ channels.
PIP2 is identified as an important regulator of cardiac Na+,Ca2+ exchange and KATP potassium channels, mediating the activating effect of ATP.
Cardiac Na + ,Ca 2+ 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 (PIP 2 ) 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 PIP 2 -specific PLC; and it was mimicked by exogenous PIP 2 . High concentrations of free Ca 2+ (5 to 20 μM) accelerated reversal of the ATP effect, and PLC activity in myocyte membranes was activated with a similar Ca 2+ dependence. Aluminum reversed the ATP effect by binding with high affinity to PIP 2 . ATP-inhibited potassium channels (K ATP ) were also sensitive to PIP 2 , whereas Na + ,K + pumps and Na + channels were not. Thus, PIP 2 may be an important regulator of both ion transporters and channels.
Hilgemann et al. (1996) studied Cardiac ion channel regulation. Phosphatidylinositol-4,5-bisphosphate (PIP2) was evaluated on Activation of cardiac Na+,Ca2+ exchange and KATP channels. Phosphatidylinositol-4,5-bisphosphate (PIP2) generated by ATP hydrolysis regulates cardiac Na+,Ca2+ exchange and ATP-inhibited potassium channels, but not Na+,K+ pumps or Na+ channels.