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Transmural Gradients in Na/K Pump Activity and [Na⁺]_i in Canine Ventricle

Department of Physiology & Biophysics, State University of New York at Stony Brook, Stony Brook, NY

Correspondence: Address reprint requests to R. T. Mathias, Tel.: 631-444-3041; Fax: 631-444-3432; E-mail: richard.mathias{at}sunysb.edu.

There are well-documented differences in ion channel activity and action potential shape between epicardial (EPI), midmyocardial (MID), and endocardial (ENDO) ventricular myocytes. The purpose of this study was to determine if differences exist in Na/K pump activity. The whole cell patch-clamp was used to measure Na/K pump current (I_P) and inward background Na⁺-current (I_inb) in cells isolated from canine left ventricle. All currents were normalized to membrane capacitance. I_P was measured as the current blocked by a saturating concentration of dihydro-ouabain. [Na⁺]_i was measured using SBFI-AM. I_P(ENDO) (0.34 ± 0.04 pA/pF, n = 17) was smaller than I_P(EPI) (0.68 ± 0.09 pA/pF, n = 38); the ratio was 0.50 with I_P(MID) being intermediate (0.53 ± 0.13 pA/pF, n = 19). The dependence of I_P on [Na⁺]_i or voltage was essentially identical in EPI and ENDO (half-maximal activation at 9–10 mM [Na⁺]_i or –90 mV). Increasing [K⁺]_o from 5.4 to 15 mM caused both I_P(ENDO) and I_P(EPI) to increase, but the ratio remained 0.5. I_inb in EPI and ENDO were nearly identical (0.6 pA/pF). Physiological [Na⁺]_i was lower in EPI (7 ± 2 mM, n = 31) than ENDO (12 ± 3 mM, n = 29), with MID being intermediate (9 ± 3 mM, n = 22). When cells were paced at 2 Hz, [Na⁺]_i increased but the differences persisted (ENDO 14 ± 3 mM, n = 10; EPI 9 ± 2 mM, n = 10; and MID intermediate, 11 ± 2 mM, n = 9). Based on these results, the larger I_P in EPI appears to reflect a higher maximum turnover rate, which implies either a larger number of active pumps or a higher turnover rate per pump protein. The transmural gradient in [Na⁺]_i means physiological I_P is approximately uniform across the ventricular wall, whereas transporters that utilize the transmembrane electrochemical gradient for Na⁺, such as Na/Ca exchange, have a larger driving force in EPI than ENDO.

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