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Single‐channel recordings of a rapid delayed rectifier current in adult mouse ventricular myocytes: basic properties and effects of divalent cations
Author(s) -
Liu Gong Xin,
Zhou Jun,
Nattel Stanley,
Koren Gideon
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.059303
Subject(s) - repolarization , chemistry , chinese hamster ovary cell , patch clamp , biophysics , electrophysiology , conductance , myocyte , herg , divalent , medicine , extracellular , potassium channel , endocrinology , biochemistry , biology , receptor , physics , organic chemistry , condensed matter physics
The rapidly delayed rectifier current ( I Kr ) has been described in ventricular myocytes isolated from many species, as well as from neonatal mice. However, whether I Kr is present in the adult mouse heart remains controversial. We used cell‐attached patch‐clamp recording in symmetrical K + solutions to assess the presence and behaviour of single I Kr channels in adult mouse cardiomyocytes (m I Kr ). Of 314 patches, 158 (50.1%) demonstrated m I Kr currents as compared with 131 (42.3%) for the I K1 channel. Single m I Kr channel activity was rarely observed at potentials positive to −10 mV. The slope conductance at negative potentials was 12 pS. Upon repolarization, ensemble‐averaged m I Kr showed slow deactivation with a biexponential time course. A selective I Kr blocker, E‐4031 (1 μ m ), completely blocked m I Kr channel activity. Extracellular Ca 2+ and Mg 2+ at physiological concentrations shifted the activation by ∼30 mV, accelerated deactivation kinetics, prolonged long‐closed time, and reduced open probability without affecting single‐channel conductance, suggesting a direct channel‐blocking effect in addition to well‐recognized voltage shifts. HERG subunits expressed in Chinese hamster ovary cells produced channels with properties similar to those of m I Kr , except for the more‐negative activation of the HERG channels. Despite the abundant expression of m I Kr , single‐channel events were rarely observed during action‐potential clamp and 5 μ m E‐4031 had no detectable effect on the action potential parameters, confirming that m I Kr plays at best a minor role in repolarization of adult mouse cardiomyocytes, probably because the modulatory effects of divalent cations prevent significant m I Kr opening under physiological conditions.