Action potential and plateau ionic currents in moderately and severely DOCA-salt hypertrophied rat hearts.
Ventricular hypertrophy is associated with an increase in action potential (AP) plateau amplitude and duration. In a model of cardiac hypertrophy by DOCA-pellet implantation in uninephrectomized saline-drinking rats, we have previously demonstrated that the influence of hypertrophy was to reduce Ito1 density, the process being fully reversible after elimination of DOCA pellets. In that study the decrease of Ito1 density appeared to vary from moderate reduction to complete suppression which could explain, at least in part, the AP lengthening. In the present study the effect of the degree of hypertrophy (moderate and severe hypertrophy) was investigated on rat ventricular action potential plateau amplitude and duration, high threshold calcium current, Ica-L, Na-Ca exchange current, INa-Ca, transient outward potassium current, Ito1, and sustained outward potassium current Isus. Ventricular action potentials of isolated perfused hearts were recorded by means of standard floating microelectrodes and ionic currents of single ventricular myocytes were measured using the whole-cell recording patch-clamp technique. We show that: (1) AP plateau amplitude and duration increase more markedly in severe than in moderate hypertrophy; (2) the decrease in Ito1 density is much larger in severe than in moderate hypertrophy whereas ICa-L, INa-Ca and i(sus) densities remain unaltered in either state of hypertrophy. After suppression of Ito1 by 3 mM 4-aminopyridine, action potential plateau amplitude and duration remain increased in severely hypertrophied rat hearts compared to sham rats. Therefore, although these results designate Ito1 reduction as the main cause of hypertrophy-induced AP changes, those occurring in severe hypertrophy cannot be uniquely explained by a quasi-complete extinction of Ito1.
Momtaz
A
A
Laboratoire de Cardiologie Moléculaire et Cellulaire (CNRS URA 1159), Hôpital Marie Lannelongue, Le Plessis Robinson, France.
Coulombe
A
A
Richer
P
P
Mercadier
J J
JJ
Coraboeuf
E
E
D000200:Action Potentials; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000503:physiopathology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
D007473:Ion Channels; D003900:Desoxycorticosterone; D012964:Sodium; D002118:Calcium