What question did this study set out to answer?

Determine the kinase-independent mechanism by which ATP activates cardiac Na+,Ca2+ exchange and evaluate whether PIP2 regulates cardiac ion transporters and channels.

August 16, 1996Science

Regulation of Cardiac Na + ,Ca 2+ Exchange and K ATP Potassium Channels by PIP 2

Q: What is the clinical evidence from this study?

Study design: Other. Population: Cardiac ion channel regulation. Intervention: Phosphatidylinositol-4,5-bisphosphate (PIP2). Primary outcome: Activation of cardiac Na+,Ca2+ exchange and KATP channels.

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Key result

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.

Population

Giant cardiac membrane patches and myocyte membranes

Design

Preclinical

Authors

DHDonald W. HilgemannElectrophysiology RBRebecca L. BallCarnegie Mellon University

Discussion

Member takes

Implication

No immediate clinical implications; leaves open translation of PIP2 regulation to human cardiac electrophysiology.

Key Points

Determine the kinase-independent mechanism by which ATP activates cardiac Na+,Ca2+ exchange and evaluate whether PIP2 regulates cardiac ion transporters and channels.
Assayed Na+,Ca2+ exchange activity in giant excised cardiac membrane patches during treatment with ATP, exogenous phospholipids, and specific phospholipases.
Tested the reversal of ATP-induced exchange activation using high free Ca2+ concentrations (5 to 20 μM) and aluminum.
Examined the sensitivity of KATP channels, Na+,K+ pumps, and Na+ channels to PIP2 application.
ATP stimulated Na+,Ca2+ exchange by synthesizing PIP2 from PI; the effect was blocked by PI-specific PLC, reversed by PIP2-specific PLC or aluminum, and reproduced by exogenous PIP2.
High free Ca2+ levels (5 to 20 μM) accelerated the reversal of the ATP effect in parallel with Ca2+-dependent activation of membrane PLC.
PIP2 directly influenced KATP potassium channels, whereas Na+,K+ pumps and Na+ channels were insensitive to its actions.

Structured PICO

Population

Giant cardiac membrane patches and myocyte membranes

Intervention

Application of ATP, exogenous PIP2, phospholipase C (PLC), and varying calcium concentrations

Outcome

Activity of cardiac Na+,Ca2+ exchange and KATP potassium channelssurrogate

PIP2 is identified as an important regulator of cardiac Na+,Ca2+ exchange and KATP potassium channels, mediating the activating effect of ATP.

Cite This Study

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.

synapsesocial.com/papers/6a08d68b720b08f65a5b6cd3 https://doi.org/10.1126/science.273.5277.956

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Regulation of Cardiac Na + ,Ca 2+ Exchange and K ATP Potassium Channels by PIP 2

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Regulation of Cardiac Na + ,Ca 2+ Exchange and K ATP Potassium Channels by PIP 2

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

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