What question did this study set out to answer?

Determine the molecular mechanism by which cyclic AMP-dependent protein kinase A (PKA) modulates individual cardiac potassium channels.

January 18, 1994Proceedings of the National Academy of SciencesOpen Access

Molecular basis of cardiac potassium channel stimulation by protein kinase A.

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Why the study?

Does protein kinase A (PKA) phosphorylation enhance the activity of cloned delayed rectifier K+ channels?

Population

Cloned delayed rectifier K+ channel normally expressed in cardiac atria

Comparison

Protein kinase A (PKA) phosphorylation vs Baseline/unphosphorylated state

Design

Preclinical

Authors

XHXue-Feng HuangChina Pharmaceutical University AMAnthony D. MorielliUniversity of Vermont EPE G PeraltaCentro Científico Tecnológico - La Plata

Discussion

Member takes

Implication

PKA phosphorylation may regulate cardiac K+ channels in animal models; leaves open translation to human electrophysiology or therapy.

Key Points

Determine the molecular mechanism by which cyclic AMP-dependent protein kinase A (PKA) modulates individual cardiac potassium channels.
Cloned and expressed a delayed rectifier K+ channel normally present in cardiac atria to measure responsiveness to PKA.
Conducted single-channel patch clamp electrophysiological recordings to evaluate channel gating kinetics and conductance states.
Mutated potential regulatory regions to identify essential PKA consensus phosphorylation sites on the channel protein.
Protein kinase A strongly enhanced the activity of the atrial delayed rectifier K+ channel.
Channel stimulation strictly required a single PKA consensus phosphorylation site located near the amino terminus.
Single-channel patch clamp recordings revealed that PKA phosphorylation increased the open duration that channels spend in higher conductance states.

Structured PICO

Does protein kinase A (PKA) phosphorylation enhance the activity of cloned delayed rectifier K+ channels?

Population

Cloned delayed rectifier K+ channel normally expressed in cardiac atria

Intervention

Protein kinase A (PKA) phosphorylation

Comparator

Baseline/unphosphorylated state

Outcome

Channel activity and open time in higher conductance statessurrogate

This study provides evidence that hormonal modulation of a cardiac K+ channel involves direct phosphorylation by PKA, which increases the open time in higher conductance states.

Cite This Study

Huang et al. (1994) studied this question.

synapsesocial.com/papers/6a73feaa5e45dc7750a8ca26 https://doi.org/10.1073/pnas.91.2.624

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Molecular basis of cardiac potassium channel stimulation by protein kinase A.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Molecular basis of cardiac potassium channel stimulation by protein kinase A.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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