T-tubule localization of the inward-rectifier K+ channel in mouse ventricular myocytes: a role in K+ accumulation

The properties of the slow inward ‘tail currents’ ( I tail ) 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 I tail on r...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of physiology 2001-12, Vol.537 (3), p.979-992
Main Authors: Clark, R B, Tremblay, A, Melnyk, P, Allen, B G, Giles, W R, Fiset, C
Format: Article
Language:English
Subjects:
Animals
Atrial Function
Barium Compounds - pharmacology
Chlorides - pharmacology
Electric Conductivity
Fluorescent Antibody Technique
Male
Mice
Myocardium - cytology
Myocardium - metabolism
Patch-Clamp Techniques
Potassium - metabolism
Potassium Channels, Inwardly Rectifying - antagonists & inhibitors
Potassium Channels, Inwardly Rectifying - metabolism
Reaction Time
Sodium-Calcium Exchanger - physiology
Tissue Distribution
Ventricular Function - drug effects
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The properties of the slow inward ‘tail currents’ ( I tail ) 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 I tail on repolarization to the holding potential. These currents were produced only by depolarizations: inwardly rectifying K + currents, I K1 , produced by steps to potentials negative to the holding potential, were not followed by I tail . For depolarizations of equal duration, the magnitude of I tail increased as the magnitude of outward current at the end of the depolarizing step increased. The apparent reversal potential of I tail 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. Removal of external Na + and Ca 2+ had no significant effect on the magnitude or time course of I tail . BaCl 2 (0.25 m m ), which had no effect on the magnitude of outward currents, abolished I tail and I K1 simultaneously. Accordingly, I tail 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 ( E K ) from its ‘resting’ value (close to −80 mV) to more depolarized potentials. This suggests that I tail is produced by I K1 in the t-tubules and is inward because of the transiently elevated K + concentration and depolarized value of E K in the t-tubules. Additional evidence for the localization of I K1 channels in the t-tubules was provided by confocal microscopy using a specific antibody against Kir2.1 in mouse ventricular myocytes.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.2001.012708