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Na/K Pump-Induced [Na]_i Gradients in Rat Ventricular Myocytes Measured with Two-Photon Microscopy

Department of Physiology, Loyola University Chicago, Maywood, Illinois

Correspondence: Address reprint requests to Donald M. Bers, PhD, Dept. of Physiology, Loyola University Chicago, 2160 South First Ave., Maywood, IL 60153. Tel.: 708-216-1018; Fax: 708-216-6308; E-mail: dbers{at}lumc.edu.

Via the Na/Ca and Na/H exchange, intracellular Na concentration ([Na]_i) is important in regulating cardiac Ca and contractility. Functional data suggest that [Na]_i might be heterogeneous in myocytes that are not in steady state, but little direct spatial information is available. Here we used two-photon microscopy of SBFI to spatially resolve [Na]_i in rat ventricular myocytes. In vivo calibration yielded an apparent K_d of 27 ± 2 mM Na. Similar resting [Na]_i was found using two-photon or single-photon ratiometric measurements with SBFI (10.8 ± 0.7 vs. 11.1 ± 0.7mM). To assess longitudinal [Na]_i gradients, Na/K pumps were blocked at one end of the myocyte (locally pipette-applied K-free extracellular solution) and active in the rest of the cell. This led to a marked increase in [Na]_i at sites downstream of the pipette (where Na enters the myocyte and Na/K pumps are blocked). [Na]_i rise was smaller at upstream sites. This resulted in sustained [Na]_i gradients (up to 17 mM/120 µm cell length). This implies that Na diffusion in cardiac myocytes is slow with respect to trans-sarcolemmal Na transport rates, although the mechanisms responsible are unclear. A simple diffusion model indicated that such gradients require a Na diffusion coefficient of 10–12 µm²/s, significantly lower than in aqueous solutions.

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