The Relationship between Frequency Dependence of Action Potential Duration and the Expression of TRPC3 in Rabbit Ventricular Myocardium

Abstract

Background/Aims: Cardiac action potential duration (APD) is regulated by heart rate, leading to the trans-membrane movement of inorganic ions. Whether the alteration of heart rate can affect the expression of transient receptor potential canonical channels (TRPCs), further studies should be made. We investigated the changes of APD at different stimulus frequencies and their influences on the expression of TRPCs in rabbit ventricular myocardium. Methods: Monophasic action potential (MAP) was recorded by contact electrode technique in different programmed stimulus frequencies on rabbit ventricular epicardium in vivo, and the expression of TRPCs was detected using RT-PCR and Western blot. Results: At the frequency range of 4.5-7.5 Hz, APD gradually shortened with the increase of stimulus frequency, showing the property of significant frequency dependence in rabbit ventricular myocardium in vivo. Compared with 4.5 Hz group, TRPC3 mRNA and protein expression increased in 6 Hz and 7.5 Hz groups by way of frequency dependence. Both amiodarone (AM) and neferine (Nef) could prolongate APD and showed characters of frequency independence at the designed frequency. In contrast with 4.5 Hz control group, it was Nef treatment group rather than AM treatment group that could obviously increase the expression of TRPC3 mRNA and protein. Conclusions: At the frequency range of 4.5-7.5 Hz, frequency-dependent shortening of APD was associated with the expression of TRPC3. AM and Nef exhibited frequency-independent lengthening of the APD. Nef may prolong APD via the increasement of TRPC3.