Heart failure in rabbit sinoatrial node cells significantly reduced the frequency of spontaneous intracellular Ca2+ transients to 3.0 Hz compared to 3.4 Hz in control cells.
In a rabbit model of heart failure, SAN cells exhibit a slower [Ca2+]i transient decay with limited effects on pacemaker activity, though reduced late diastolic [Ca2+]i rise during β-adrenergic stimulation may impair intrinsic frequency increases.
Absolute Event Rate: 3% vs 3.4%
p-value: p=<0.05
BACKGROUND: In animal models of heart failure (HF), heart rate decreases due to an increase in intrinsic cycle length (CL) of the sinoatrial node (SAN). Pacemaker activity of SAN cells is complex and modulated by the membrane clock, i.e., the ensemble of voltage gated ion channels and electrogenic pumps and exchangers, and the Ca(2+) clock, i.e., the ensemble of intracellular Ca(2+) (Ca(2+)i) dependent processes. HF in SAN cells results in remodeling of the membrane clock, but few studies have examined its effects on Ca(2+)i homeostasis. METHODS: SAN cells were isolated from control rabbits and rabbits with volume and pressure overload-induced HF. Ca(2+)i concentrations, and action potentials (APs) and Na(+)-Ca(2+) exchange current (INCX) were measured using indo-1 and patch-clamp methodology, respectively. RESULTS: The frequency of spontaneous Ca(2+)i transients was significantly lower in HF SAN cells (3.0 ± 0.1 (n = 40) vs. 3.4 ± 0.1 Hz (n = 45); mean ± SEM), indicating that intrinsic CL was prolonged. HF slowed the Ca(2+)i transient decay, which could be explained by the slower frequency and reduced sarcoplasmic reticulum (SR) dependent rate of Ca(2+) uptake. Other Ca(2+)i transient parameters, SR Ca(2+) content, INCX density, and INCX-Ca(2+)i relationship were all unaffected by HF. Combined AP and Ca(2+)i recordings demonstrated that the slower Ca(2+)i transient decay in HF SAN cells may result in increased INCX during the diastolic depolarization, but that this effect is likely counteracted by the HF-induced increase in intracellular Na(+). β-adrenergic and muscarinic stimulation were not changed in HF SAN cells, except that late diastolic Ca(2+)i rise, a prominent feature of the Ca(2+) clock, is lower during β-adrenergic stimulation. CONCLUSIONS: HF SAN cells have a slower Ca(2+)i transient decay with limited effects on pacemaker activity. Reduced late diastolic Ca(2+)i rise during β-adrenergic stimulation may contribute to an impaired increase in intrinsic frequency in HF SAN cells.
Verkerk et al. (Mon,) conducted a other in Heart failure (n=25). Volume and pressure overload-induced heart failure vs. Age-matched non-operated healthy controls was evaluated on Frequency of spontaneous [Ca2+]i transients (Hz) (p=<0.05). Heart failure in rabbit sinoatrial node cells significantly reduced the frequency of spontaneous intracellular Ca2+ transients to 3.0 Hz compared to 3.4 Hz in control cells.