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1 Ullevaal University Hospital, Institute for Experimental Medical Research, Oslo, Norway; University of Oslo, Center for Heart Failure Research, Oslo, Norway
2 University of Oslo, Center for Heart Failure Research, Oslo, Norway; Ullevaal University Hospital, Institute for Experimental Medical Research, Oslo, Norway
3 Ullevaal University Hospital, Institute for Experimental Medical Research, Oslo, Norway; University of Oslo, Center for Heart Failure Research, Oslo, Norway; Ullevaal University Hospital, Department of Cardiology, Oslo, Norway
* To whom correspondence should be addressed. E-mail: fredrik.swift{at}medisin.uio.no.
Cardiomyocyte contractility is regulated by the extracellular K+ concentration ([K+]o). Potassium dynamics in the t-tubules during the excitation-contraction cycle depends on the diffusion rate of K+, but this rate is not known. Detubulation of rat cardiomyocytes was induced by osmotic shock using formamide, which separated the surface membrane from the t-tubules. Change in current and membrane potential in voltage clamped (-80 mV) and current clamped control and detubulated cardiomyocytes were compared during rapid switches between 5.4 mM and 8.1 mM [K+]o, and the results were simulated in a mathematical model. In the voltage clamp experiments, the current changed significantly slower in control than in detubulated cardiomyocytes during the switch from 5.4 mM to 8.1 mM [K+]o, indicated by the times to achieve 25%, 50%, 90% and 95% of the steady state current (control (ms) t25=98 ± 12, t50=206 ± 20, t90=570 ± 72, t95=666 ± 92; detubulated t25=61 ± 11, t50=142 ± 17, t90=352 ± 52, t95=420 ± 69). These time points were not significantly different either during the 8.1 mM to 5.4 mM [K+]o switch, or in current clamped cardiomyocytes switching from 5.4 mM to 8.1 mM [K+]o. Mathematical simulation of the difference current between control and detubulated cardiomyocytes gave a t-tubular diffusion rate for K+ of ~85 µm2.s-1. We conclude that the diffusion of K+ in the t-tubules is so slow that they constitute a functional compartment. This might play a key role in local regulation of the action potential, and thus in the regulation of cardiomyocyte contractility.
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