What question did this study set out to answer?

To determine how intracellular free magnesium modulates L-type calcium currents in ventricular cardiomyocytes under basal conditions, protein kinase inhibition, and cAMP-mediated stimulation.

October 1, 2001AJP Heart and Circulatory Physiology

Phosphorylation-dependent modulation of cardiac calcium current by intracellular free magnesium

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To determine how intracellular free magnesium modulates L-type calcium currents in ventricular cardiomyocytes under basal conditions, protein kinase inhibition, and cAMP-mediated stimulation.
Recorded L-type calcium currents (I_Ca,L) in isolated guinea pig ventricular cardiomyocytes using whole-cell patch-clamp electrophysiology across intracellular magnesium concentrations from 10⁻⁶ to 10⁻² M.
Evaluated current dynamics under baseline conditions, in the presence of 10 µM K252a to inhibit protein kinases, and following maximal stimulation of cAMP-mediated phosphorylation.
Basal I_Ca,L density exhibited a bimodal response to intracellular magnesium, peaking at approximately 20 µM before declining steeply at higher concentrations.
Inhibition of protein kinases with K252a reduced overall I_Ca,L density and abolished both the stimulatory and inhibitory effects of intracellular magnesium, sparing only a negative shift in current-voltage relations.
Maximal cAMP stimulation prevented magnesium-induced current enhancement and blocked magnesium-mediated current inhibition at concentrations below 1 mM.

Structured PICO

Population

Patch-clamped guinea pig ventricular cardiomyocytes

Intervention

Varying concentrations of cytosolic free magnesium (Mg(2+)(i)) (10(-6)-10(-2) M) under basal conditions, after inhibition of protein phosphorylation (K252a 10 microM), and after stimulation of cAMP-mediated phosphorylation

Comparator

Different concentrations of Mg(2+)(i) and basal conditions

Outcome

L-type Ca(2+) current (I(Ca,L)) densitysurrogate

Modulation of cardiac L-type calcium current by intracellular free magnesium is dependent on protein kinase activity and interacts with cAMP-mediated phosphorylation.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Protein kinase dependence of Mg effects on cardiac Ca current remains preclinical; extends mechanistic insight but leaves clinical relevance open.

Cite This Study

Pelzer et al. (2001) studied this question.

synapsesocial.com/papers/6a88277b951efdbb75f4c9cc https://doi.org/10.1152/ajpheart.2001.281.4.h1532

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Implication

Protein kinase dependence of Mg effects on cardiac Ca current remains preclinical; extends mechanistic insight but leaves clinical relevance open.

Phosphorylation-dependent modulation of cardiac calcium current by intracellular free magnesium

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Phosphorylation-dependent modulation of cardiac calcium current by intracellular free magnesium

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider