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Relationship between K + channel down‐regulation and [Ca 2+ ] i in rat ventricular myocytes following myocardial infarction
Author(s) -
Kaprielian R.,
Wickenden A. D.,
Kassiri Z.,
Parker T. G.,
Liu P. P.,
Backx* P. H.
Publication year - 1999
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 - 10.1111/j.1469-7793.1999.0229z.x
Subject(s) - myocyte , medicine , cardiac transient outward potassium current , endocrinology , patch clamp , cardiology , inward rectifier potassium ion channel , chemistry , endoplasmic reticulum , membrane potential , myocardial infarction , potassium channel , electrophysiology , ion channel , biochemistry , receptor
1 Cardiac hypertrophy and prolongation of the cardiac action potential are hallmark features of heart disease. We examined the molecular mechanisms and the functional consequences of this action potential prolongation on calcium handling in right ventricular myocytes obtained from rats 8 weeks following ligation of the left anterior descending coronary artery (post‐myocardial infarction (MI) myocytes). 2 Compared with myocytes from sham‐operated rats (sham myocytes), post‐MI myocytes showed significant reductions in transient outward K + current ( I to ) density (sham 19·7 ± 1·1 pA pF −1 versus post‐MI 11·0 ± 1·3 pA pF −1 ; means ± s.e.m.), inward rectifier K + current density (sham ‐13·7 ± 0·6 pA pF −1 versus post‐MI ‐10·3 ± 0·9 pA pF −1 ) and resting membrane potential (sham ‐84·4 ± 1·3 mV versus post‐MI ‐74·1 ± 2·6 mV). Depressed I to amplitude correlated with significant reductions in Kv4.2 and Kv4.3 mRNA and Kv4.2 protein levels. Kv1.4 mRNA and protein levels were increased and coincided with the appearance of a slow component of recovery from inactivation for I to . 3 In current‐clamp recordings, post‐MI myocytes showed a significant increase in [Ca 2+ ] i transient amplitude compared with sham myocytes. Using voltage‐clamp depolarizations, no intrinsic differences in Ca 2+ handling by the sarcoplasmic reticulum or in L‐type Ca 2+ channel density ( I Ca,L ) were detected between the groups. 4 Stimulation of post‐MI myocytes with an action potential derived from a sham myocyte reduced the [Ca 2+ ] transient amplitude to the sham level and vice versa. 5 The net Ca 2+ influx per beat via I Ca,L was increased about 2‐fold in myocytes stimulated with post‐MI action potentials compared with sham action potentials. 6 Our findings demonstrate that reductions in K + channel expression in post‐MI myocytes prolong action potential duration resulting in elevated Ca 2+ influx and [Ca 2+ ] i transients.