Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / pharmacology
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Aluminum / metabolism
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Aluminum / pharmacology
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Animals
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Calcium / metabolism*
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Calcium / pharmacology
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Carrier Proteins / metabolism
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Guinea Pigs
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Myocardium / cytology
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Myocardium / metabolism*
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Patch-Clamp Techniques
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Phosphatidylinositol 4,5-Diphosphate
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Phosphatidylinositol Phosphates / metabolism*
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Phosphatidylinositol Phosphates / pharmacology
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Phosphatidylinositols / metabolism
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Potassium Channel Blockers
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Potassium Channels / metabolism*
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Sodium / metabolism*
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Sodium-Calcium Exchanger
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Type C Phospholipases / metabolism
Substances
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Carrier Proteins
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Phosphatidylinositol 4,5-Diphosphate
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Phosphatidylinositol Phosphates
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Phosphatidylinositols
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Potassium Channel Blockers
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Potassium Channels
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Sodium-Calcium Exchanger
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Adenosine Triphosphate
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Sodium
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Aluminum
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Type C Phospholipases
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Calcium