Swift, Fredrik, Taevje A. Strømme, Bjørn Amundsen, Ole M. Sejersted, and Ivar Sjaastad. Slow diffusion of K ϩ in the T tubules of rat cardiomyocytes. diomyocyte contractility is regulated by the extracellular K ϩ concentration ([K ϩ ]o). Potassium dynamics in the T tubules during the excitation-contraction cycle depends on the diffusion rate of K ϩ , but this rate is not known. Detubulation of rat cardiomyocytes was induced by osmotic shock using formamide, which separated the surface membrane

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... rom the T tubules. Changes in current and membrane potential in voltage-clamped (Ϫ80 mV) and current-clamped control and detubulated cardiomyocytes were compared during rapid switches between 5.4 and 8.1 mM [K ϩ ]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 to 8.1 mM [K ϩ ]o, as indicated by the times to achieve 25, 50, 90, and 95% of the new steady-state current [control (ms) t25 ϭ 98 Ϯ 12, t50 ϭ 206 Ϯ 20, t90 ϭ 570 Ϯ 72, t95 ϭ 666 Ϯ 92; detubulated t25 ϭ 61 Ϯ 11, t50 ϭ 142 Ϯ 17, t90 ϭ 352 Ϯ 52, t95 ϭ 420 Ϯ 69]. These time points were not significantly different either during the 8.1 to 5.4 mM [K ϩ ]o switch or in current-clamped cardiomyocytes switching from 5.4 to 8.1 mM [K ϩ ]o. Mathematical simulation of the difference current between control and detubulated cardiomyocytes gave a t-tubular diffusion rate for K ϩ of ϳ85 m 2 /s. We conclude that the diffusion of K ϩ 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. mathematical model; detubulation; rapid perfusion; electrophysiology