TY - JOUR
T1 - Regulation of cardiac Na+,Ca2+ exchange and K(ATP) potassium channels by PIP2
AU - Hilgemann, Donald W.
AU - Ball, Rebecca
PY - 1996/8/16
Y1 - 1996/8/16
N2 - 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 μM) 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 (K(ATP)) 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.
AB - 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 μM) 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 (K(ATP)) 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.
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U2 - 10.1126/science.273.5277.956
DO - 10.1126/science.273.5277.956
M3 - Article
C2 - 8688080
AN - SCOPUS:0029831984
SN - 0036-8075
VL - 273
SP - 956
EP - 959
JO - Science
JF - Science
IS - 5277
ER -