Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart

Article

关键词: RENIN-ANGIOTENSIN SYSTEM;    PROTEIN-KINASE-C;    T-WAVE CHANGES;    ACTIVATION;    EVOLUTION;    MYOCYTES;    APLYSIA;   

DOI  :  10.1161/01.CIR.0000068376.88600.41

来源: SCIE

【 摘 要 】

Background-We tested the hypothesis that I-Ca,I-L is important to the development of cardiac memory. Methods and Results-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. AT(1) 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 I-Ca,I-L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by I-Ca,I-L blockers but not beta-blockers. Neither AT(1) 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 I-Ca,I-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-I-Ca,I-L blockade but not β-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered I-Ca,I-L kinetics.

【 授权许可】

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