T‐tubule localization of the inward‐rectifier K+ channel in mouse ventricular myocytes: a role in K+ accumulation
RB Clark, A Tremblay, P Melnyk… - The Journal of …, 2001 - Wiley Online Library
The Journal of physiology, 2001•Wiley Online Library
1 The properties of the slow inward 'tail currents'(Itail) that followed depolarizing steps in
voltage‐clamped, isolated mouse ventricular myocytes were examined. Depolarizing steps
that produced large outward K+ currents in these myocytes were followed by a slowly
decaying inward Itail on repolarization to the holding potential. These currents were
produced only by depolarizations: inwardly rectifying K+ currents, IK1, produced by steps to
potentials negative to the holding potential, were not followed by Itail. 2 For depolarizations …
voltage‐clamped, isolated mouse ventricular myocytes were examined. Depolarizing steps
that produced large outward K+ currents in these myocytes were followed by a slowly
decaying inward Itail on repolarization to the holding potential. These currents were
produced only by depolarizations: inwardly rectifying K+ currents, IK1, produced by steps to
potentials negative to the holding potential, were not followed by Itail. 2 For depolarizations …
- 1The properties of the slow inward ‘tail currents’ (Itail) that followed depolarizing steps in voltage‐clamped, isolated mouse ventricular myocytes were examined. Depolarizing steps that produced large outward K+ currents in these myocytes were followed by a slowly decaying inward Itail on repolarization to the holding potential. These currents were produced only by depolarizations: inwardly rectifying K+ currents, IK1, produced by steps to potentials negative to the holding potential, were not followed by Itail.
- 2For depolarizations of equal duration, the magnitude of Itail increased as the magnitude of outward current at the end of the depolarizing step increased. The apparent reversal potential of Itail was dependent upon the duration of the depolarizing step, and the reversal potential shifted to more depolarized potentials as the duration of the depolarization was increased.
- 3Removal of external Na+ and Ca2+ had no significant effect on the magnitude or time course of Itail. BaCl2 (0.25 mm), which had no effect on the magnitude of outward currents, abolished Itail and IK1 simultaneously.
- 4Accordingly, Itail in mouse ventricular myocytes probably results from K+ accumulation in a restricted extracellular space such as the transverse tubule system (t‐tubules). The efflux of K+ into the t‐tubules during outward currents produced by depolarization shifts the K+ Nernst potential (EK) from its ‘resting’ value (close to −80 mV) to more depolarized potentials. This suggests that Itail is produced by IK1 in the t‐tubules and is inward because of the transiently elevated K+ concentration and depolarized value of EK in the t‐tubules.
- 5Additional evidence for the localization of IK1 channels in the t‐tubules was provided by confocal microscopy using a specific antibody against Kir2.1 in mouse ventricular myocytes.
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