Biophys J, March 2001, p. 1230-1237, Vol. 80, No. 3

The Sodium Pump Modulates the Influence of I_Na on [Ca²⁺]_i Transients in Mouse Ventricular Myocytes

Zhi Su,^* Kazuro Sugishita,^* Michael Ritter,^* Fenghua Li,^* Kenneth W. Spitzer, and William H. Barry^*

 ^*Cardiology Division and  Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah Health Sciences Center, Salt Lake City, Utah 84132 USA

To investigate whether activity of the sarcolemmal Na pump modulates the influence of sodium current on excitation-contraction (E-C) coupling, we measured [Ca²⁺]_i transients (fluo-3) in single voltage-clamped mouse ventricular myocytes ([Na⁺]_pip = 15 or 0 mM) when the Na pump was activated (4.4 mM K) and during abrupt inhibition of the pump by exposure to 0 K with a rapid solution-switcher device. After induction of steady state [Ca²⁺]_i transients by conditioning voltage pulses (0.25 Hz), inhibition of the Na pump for 1.5 s immediately before and continuing during a voltage pulse (200 ms, 80 to 0 mV) caused a significant increase (15 ± 2%; n = 16; p < 0.01) in peak systolic [Ca²⁺]_i when [Na⁺]_pip was 15 mM. In the absence of sodium current (I_Na, which was blocked by 60 µM tetrodotoxin (TTX)), inhibition of the Na pump immediately before and during a voltage pulse did not result in an increase in peak systolic [Ca²⁺]_i. Abrupt blockade of I_Na during a single test pulse with TTX caused a slight decrease in peak [Ca²⁺]_i, whether the pump was active (9%) or inhibited (10%). With the reverse-mode Na/Ca exchange inhibited by KB-R 7943, inhibition of the Na pump failed to increase the magnitude of the peak systolic [Ca²⁺]_i (4 ± 1%; p = NS) when [Na⁺]_pip was 15 mM. When [Na⁺]_pip was 0 mM, the amplitude of the peak systolic [Ca²⁺]_i was not altered by abrupt inhibition of the Na pump immediately before and during a voltage pulse. These findings in adult mouse ventricular myocytes indicate the Na pump can modulate the influence of I_Na on E-C coupling in a single beat and provide additional evidence for the existence of Na fuzzy space, where [Na⁺] can significantly modulate Ca²⁺ influx via reverse Na/Ca exchange.

Biophys J, March 2001, p. 1230-1237, Vol. 80, No. 3
© 2001 by the Biophysical Society   0006-3495/01/03/1230/08  $2.00

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