What question did this study set out to answer?

To determine how ATP depletion via metabolic inhibition and intracellular free magnesium regulate voltage-gated calcium channel currents in cerebral vascular smooth muscle cells.

April 15, 1996The Journal of PhysiologyOpen Access

Modulation of Ca2+ channel activity by ATP metabolism and internal Mg2+ in guinea‐pig basilar artery smooth muscle cells.

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Population

Single smooth muscle cells isolated from the basilar artery of the guinea-pig

Comparison

Bath application of metabolic inhibitors and… vs Baseline or control conditions

Design

Preclinical

Authors

DMDamian McHughAdvisory Board Company (United States)DBDavid J. BeechVascular / Pulmonary Vascular

Discussion

Member takes

Implication

Mitochondrial ATP inhibition effects on Ca2+ currents remain preclinical; leaves open relevance to cerebral vasomotor control or therapeutic targets.

Key Points

To determine how ATP depletion via metabolic inhibition and intracellular free magnesium regulate voltage-gated calcium channel currents in cerebral vascular smooth muscle cells.
Isolated single smooth muscle cells from guinea-pig basilar arteries and recorded calcium channel currents using amphotericin-perforated and conventional whole-cell patch-clamp techniques within 10 hours of isolation.
Applied mitochondrial uncouplers (2,4-dinitrophenol, rotenone) or glycolytic blockers (2-deoxy-D-glucose) and manipulated internal ATP and free Mg2+ levels to assess channel kinetics and activation curves.
Mitochondrial uncoupling by 2,4-dinitrophenol elicited biphasic modulation of Ca2+ current, producing an initial 14% stimulation (in 5 of 11 cells) with a -9 mV activation curve shift, followed by a 50% inhibition (in 9 of 11 cells within 9.5 minutes), while glycolytic inhibition showed negligible effect.
Intracellular free Mg2+ inhibited current through calcium channels in the absence of ATP with a dissociation constant of approximately 100 µM at -10 mV and shifted the activation curve to more negative potentials, mimicking mitochondrial poisoning.

Structured PICO

Population

Single smooth muscle cells isolated from the basilar artery of the guinea-pig

Intervention

Bath application of metabolic inhibitors (2,4-dinitrophenol, 2-deoxy-D-glucose, rotenone) and manipulation of intracellular Mg2+ and ATP

Comparator

Baseline or control conditions (e.g., absence of metabolic inhibitors, presence of ATP)

Outcome

Voltage-dependent Ca2+ current (I(Ca)) and Na+ current through Ca2+ channels (I[(Ca)(Na)])surrogate

Inhibition of mitochondrial ATP production modulates voltage-gated Ca2+ channels in basilar artery smooth muscle cells, an effect that may be coupled by intracellular free Mg2+ concentration.

Cite This Study

McHugh et al. (1996) studied this question.

synapsesocial.com/papers/6a75b2dcae41e4ffbd6a3ade https://doi.org/10.1113/jphysiol.1996.sp021314

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Implication

Mitochondrial ATP inhibition effects on Ca2+ currents remain preclinical; leaves open relevance to cerebral vasomotor control or therapeutic targets.

Modulation of Ca2+ channel activity by ATP metabolism and internal Mg2+ in guinea‐pig basilar artery smooth muscle cells.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Modulation of Ca2+ channel activity by ATP metabolism and internal Mg2+ in guinea‐pig basilar artery smooth muscle cells.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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