What question did this study set out to answer?

Investigate how L-type Ca2+ channels and reverse-mode Na+-Ca2+ exchange interact to trigger sarcoplasmic reticulum Ca2+ release in normal versus failing rat cardiomyocytes.

June 24, 2005The Journal of PhysiologyOpen Access

Synergistic interactions between Ca²⁺ entries through L‐type Ca²⁺ channels and Na⁺–Ca²⁺ exchanger in normal and failing rat heart

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Population

Cardiac myocytes from normal and failing rat hearts

Comparison

Protein kinase A stimulation using db-cAMP, and… vs Absence of PKA stimulation; normal versus…

Design

Preclinical

Authors

SVSerge Viatchenko‐KarpinskiUnited States Food and Drug Administration DTDmitry TerentyevNew Jersey Institute of Technology LJLeigh Ann JenkinsTexas Tech University

Discussion

Member takes

Implication

May explain contractile impairment in heart failure; leaves open whether restoring synergy offers therapeutic targets.

Key Points

Investigate how L-type Ca2+ channels and reverse-mode Na+-Ca2+ exchange interact to trigger sarcoplasmic reticulum Ca2+ release in normal versus failing rat cardiomyocytes.
Used patch-clamp electrophysiology and confocal Ca2+ imaging to record cytosolic Ca2+ transients and membrane potentials in isolated rat ventricular myocytes.
Administered db-cAMP to stimulate protein kinase A (PKA) and isolated specific influx pathways using nifedipine (LCC blocker) and KB-R7943 (reverse-mode NCX blocker).
In normal myocytes stimulated by PKA, total Ca2+ influx at positive membrane potentials became approximately threefold larger than the arithmetic sum of independent LCC- and NCX-mediated entries.
In failing myocytes, PKA stimulation did not broaden the voltage dependence of Ca2+ release, and total Ca2+ influx did not significantly exceed the sum of individual LCC and NCX components.

Structured PICO

Population

Cardiac myocytes from normal and failing rat hearts

Intervention

Protein kinase A (PKA) stimulation using db-cAMP, and exposure to specific inhibitors (nifedipine for L-type Ca2+ channels, KB-R7943 for reverse-mode Na+-Ca2+ exchange)

Comparator

Absence of PKA stimulation; normal versus failing myocytes

Outcome

Trans-sarcolemmal Ca2+ entries and voltage dependence of Ca2+-induced Ca2+ release (CICR)surrogate

The synergistic interaction between L-type Ca2+ channels and the Na+-Ca2+ exchanger in triggering sarcoplasmic reticulum Ca2+ release is diminished in heart failure, potentially explaining reduced contractile performance.

Cite This Study

Viatchenko‐Karpinski et al. (2005) studied this question.

synapsesocial.com/papers/6a884d133ef9a64eb0cf029b https://doi.org/10.1113/jphysiol.2005.091280

Topics

Cardiomyopathy

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Synergistic interactions between Ca²⁺ entries through L‐type Ca²⁺ channels and Na⁺–Ca²⁺ exchanger in normal and failing rat heart

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Synergistic interactions between Ca²⁺ entries through L‐type Ca²⁺ channels and Na⁺–Ca²⁺ exchanger in normal and failing rat heart

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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