Increasing T-Type calcium channel activity by β-adrenergic stimulation contributes to β-adrenergic regulation of heart rates

Abstract

Objective

Cav3.1 (α_1G) T-type Ca²⁺ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular nodal (AVN) cells and contributes to heart rate genesis and AV conduction. However, its role in heart rate (HR) regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear, which is the topic of this study.

Methods and Results

L- (I_Ca-L) and T-type (I_Ca-T) Ca²⁺ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. I_Ca-T was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of ISO were infused through jugular vein and the heart rate was recorded. The EC₅₀ of HR response to isoproterenol was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by isoproterenol was greater in TG mice but less in KO mice. In Langendorff-perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after isoproterenol; TG SANCs had similar basal beating rates as control SANCs probably due to decreased I_Ca-L but greater response to isoproterenol than control SANCs. I_Ca-T in SANCs was significantly increased by isoproterenol.

Conclusion

I_Ca-T upregulation by β-adrenergic stimulation contributes to HR and conduction regulation by the SAS. TTCC can be a target for slowing heart rates.

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