What question did this study set out to answer?

Determine whether the maximum upstroke velocity of action potentials (Vmax) reliably predicts peak sodium current (INa) and sodium channel availability in cardiac Purkinje cells.

August 1, 1988Circulation Research

Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells.

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Determine whether the maximum upstroke velocity of action potentials (Vmax) reliably predicts peak sodium current (INa) and sodium channel availability in cardiac Purkinje cells.
Recorded action potentials and peak INa using voltage clamp in single, internally perfused canine cardiac Purkinje cells under conditions where action potentials depended solely on INa.
Modulated sodium channel availability using voltage-dependent inactivation, tetrodotoxin (TTX) block, and use-dependent block via quinidine across varying experimental temperatures.
The relationship between Vmax and INa was consistently nonlinear across all interventions, preventing accurate calculation or prediction of INa from Vmax measurements.
Vmax overestimated channel availability during voltage-dependent inactivation and TTX block due to channel mobilization during slowed upstrokes, yielding an apparent TTX dissociation constant (Kd) of 4.5 µM compared to 1.6 µM measured directly with INa.
Quinidine block exhibited marked voltage dependence under voltage clamp that was obscured during action potentials, causing Vmax to unpredictably underestimate or overestimate drug block.

Structured PICO

Population

Single, internally perfused, canine cardiac Purkinje cells

Intervention

Alteration of sodium channel availability via voltage-dependent inactivation, tetrodotoxin (TTX) block, and use-dependent block by quinidine

Outcome

Relation of the maximal upstroke velocity (Vmax) of action potentials to the peak sodium current (INa)surrogate

Vmax is a convenient index for INa but is not a reliable method for quantitative studies of sodium channel behavior due to its nonlinear relationship and overestimation of channel availability.

Discussion

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Implication

Vmax should not quantify INa availability in sodium channel studies; leaves open its qualitative use for conduction in intact preparations.

Cite This Study

Sheets et al. (1988) studied this question.

synapsesocial.com/papers/6a7ba96b01db1a7270ed1ecf https://doi.org/10.1161/01.res.63.2.386

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Implication

Vmax should not quantify INa availability in sodium channel studies; leaves open its qualitative use for conduction in intact preparations.

Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells.

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells.

Key Points

Structured PICO

Discussion

Implication

Cite This Study

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