Key result
Overexpression of CLOCK-BMAL1 significantly reduced peak L-type calcium current densities (1.41 vs 3.22) and CACNA1C expression in cardiomyocytes, an effect abolished by Akt or PDK1 inhibitors.
Why the study?
Does CLOCK-BMAL1 overexpression regulate CACNA1C expression and L-type calcium currents in isolated guinea pig cardiomyocytes?
Does CLOCK-BMAL1 overexpression regulate CACNA1C expression and L-type calcium currents in isolated guinea pig cardiomyocytes?
CLOCK-BMAL1 heterodimers regulate the expression and function of the cardiac L-type calcium channel subunit CACNA1C via the PI3K-Akt signaling pathway, providing insight into the circadian regulation of cardiac electrophysiology.
Answers are grounded in this paper and cite their sources.
Suggests circadian clock involvement in cardiac calcium handling; leaves open whether this influences arrhythmia risk or therapy in vivo.
The heterodimerized transcription factors CLOCK-BMAL1 regulate the cardiomyocyte circadian rhythms. The L-type calcium currents play important role in the cardiac electrogenesis and arrhythmogenesis. Whether and how the CLOCK-BMAL1 regulate the cardiac L-type calcium channels are yet to be determined. The functions of the L-type calcium channels were evaluated with patch clamping techniques. Recombinant adenoviruses of CLOCK and BMAL1 were used in the expression experiments. We reported that the expressions and functions of CACNA1C (the α-subunit of the L-type calcium channels) showed circadian rhythms, with the peak at zeitgeber time 3 (ZT3). The endocardial action potential durations 90 (APD90) were correspondingly longer at ZT3. The protein levels of the phosphorylated Akt at threonine 308 (pAkt T308) also showed circadian rhythms. Overexpressions of CLOCK-BMAL1 significantly reduced the levels of CACNA1C while increasing the levels of pAkt T308 and pik3r1. Furthermore, the inhibitory effects of CLOCK-BMAL1 on CACNA1C could be abolished by the Akt inhibitor MK2206 or the PDK1 inhibitor GSK2334470. Collectively, our findings suggested that the expressions of the cardiac CACNA1C were under the CLOCK-BMAL1 regulation, probably through the PI3K-Akt signal pathway.
No takes yet. Share an insight, caveat, or question.
Chen et al. (2016) studied Circadian rhythm regulation of cardiac electrophysiology. CLOCK-BMAL1 overexpression vs. Control adenovirus was evaluated on Peak L-type calcium current density (p=<0.05). Overexpression of CLOCK-BMAL1 significantly reduced peak L-type calcium current densities (1.41 vs 3.22) and CACNA1C expression in cardiomyocytes, an effect abolished by Akt or PDK1 inhibitors.
Synapse has enriched 10 related papers. Consider them for comparative context: