Slow diffusion of K+ in the T tubules of rat cardiomyocytes.
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. Changes 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 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 to 8.1 mM [K(+)](o), as indicated by the times to achieve 25, 50, 90, and 95% of the new steady-state current [control (ms) t(25) = 98 +/- 12, t(50) = 206 +/- 20, t(90) = 570 +/- 72, t(95) = 666 +/- 92; detubulated t(25) = 61 +/- 11, t(50) = 142 +/- 17, t(90) = 352 +/- 52, t(95) = 420 +/- 69]. These time points were not significantly different either during the 8.1 to 5.4 mM [K(+)](o) switch or in current-clamped cardiomyocytes switching from 5.4 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 approximately 85 mum(2)/s. 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.
Swift
Fredrik
F
Institute for Experimental Medical Research, Ullevaal University Hospital, Kirkeveien 166, N-0407 Oslo, Norway. fredrik.swift@medisin.uio.no
Strømme
Taevje A
TA
Amundsen
Bjørn
B
Sejersted
Ole M
OM
Sjaastad
Ivar
I
D000200:Action Potentials; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D004058:Diffusion; D004594:Electrophysiology; D066298:In Vitro Techniques; D007477:Ions; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007477:Ions; D011188:Potassium