Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart.
Circulation
; 107(22): 2844-9, 2003 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-12756152
ABSTRACT
BACKGROUND:
We tested the hypothesis that ICa,L is important to the development of cardiac memory. METHODS ANDRESULTS:
The effects of L-type Ca2+ channel blockade and beta-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days. STM dogs received placebo, nifedipine, or propranolol, and LTM dogs received placebo, atenolol, or amlodipine. AT1 receptor blockade (candesartan) and ACE inhibition (trandolapril) were also tested in LTM. Microelectrodes were used to record transmembrane potentials from isolated epicardial and endocardial slabs using a protocol simulating STM in intact animals. Left ventricular epicardial myocytes from LTM or sham control dogs were dissociated, and ICa,L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by ICa,L blockers but not beta-blockers. Neither AT1 receptor blockade nor ACE inhibition suppressed LTM. In microelectrode experiments, pacing induced an epicardial-endocardial gradient change mimicking STM that was suppressed by nifedipine. In patch-clamp experiments, peak ICa,L density in LTM and control were equivalent, but activation was more positive and time constants of inactivation longer in LTM (P<0.05).CONCLUSIONS:
ICa,L blockade but not beta-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered ICa,L kinetics.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio Tipo L
/
Coração
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos