The ionic basis for delayed after-depolarizations in cardiac hypertrophy

J. Mészáros, D. Khananshvili, G. Hart

Research output: Contribution to journalArticlepeer-review

Abstract

The transient inward current (TI) causes arrhythmias in glycoside intoxication but has not previously been investigated as a cellular mechanism for arrhythmias in cardiac hypertrophy. Therefore we have looked for arrhythmogenic delayed after-depolarizations (DADs) and TI in left ventricular myocytes isolated from rats with cardiac hypertrophy, using the whole-cell voltage-clamp technique. Male Wistar rats (HTY) received i.p. injections of 5 mg/kg/day isoprenaline for 7 days. Age-matched control rats (CON) received 0.9% NaCl solution. Data are expressed as mean±sem (n). The heart weight to body weight ratio was increased in hypertrophy (CON 3.2±0.1 mg/g (10), HTY 4.0±0.2 mg/g (10) p<0.001, Student's t-test). Cell capacity was increased and the lung weight to body weight ratio was unchanged. DADs were observed at the end of the action potential in HTY but not in CON myocytes (see fig, upper panel). TI was inducible on repolarization, after 2 s depolarizing voltage steps from a holding potential of -40 mV to +60 mV, in HTY but not in CON myocytes (see fig, lower panel). Using this protocol the density of TI was -1.69 ±0.12 pA/pF. The amplitude of TI was sensitive to the amplitude and the duration of the preceding pulse. TI was completely abolished by 10 μM ryanodine, a SR Ca2+-release channel blocker. Using selective inhibitors for Na+-Ca2+ exchange (FRCRCFa) and for the Cl- current (DIDS) we demonstrated that TI is carried principally by Na+-Ca2+ exchange (82% at -40 mV) with smaller contributions from an outward Cl- channel (5%) and from an inward non-selective cation channel (13%). These results show that DADs and TI are present in hypertrophied but not in control myocytes, and provide a cellular mechanism for triggered arrhythmias in cardiac hypertrophy. (Graph Presented).

Original languageEnglish
Pages (from-to)P60
JournalHeart
Volume79
Issue numberSUPPL. 1
StatePublished - May 1998

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