Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca2+current

Background: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through Ca(V)1.2 channels under cell stretching using the whole-cell patch-clamp method.Results: Among channels that showed mechanosensitivity, significant amounts of TRPM7, TRPC1, and TRPM4 transcripts were found. We suppose that the recorded L-type Ca2+ current is probably expressed through Ca(V)1.2. Furthermore, stretching cells by 6, 8, and 10 mu m, which increases I-SAC through the TRPM7, TRPC1, and TRPM4 channels, also decreased I-Ca,I-L through the Ca(V)1.2 channels in K+ (in)/K+ (out), Cs+ (in)/K+ (out), K+ (in)/Cs+ (out), and Cs+ (in)/Cs+ (out) solutions. The application of a nonspecific I-SAC blocker, Gd3+, during cell stretching eliminated I-SAC through nonselective cation channels and I-Ca,I-L through Ca(V)1.2 channels. Since the response to Gd3+ was maintained in Cs+ (in)/Cs+ (out) solutions, we suggest that voltage-gated Ca(V)1.2 channels in the ventricular myocytes of adult rats also exhibit mechanosensitive properties.Conclusions: Our findings suggest that TRPM7, TRPC1, and TRPM4 channels represent stretch-activated nonselective cation channels in rat ventricular myocytes. Probably the Ca(V)1.2 channels in these cells exhibit mechanosensitive properties. Our results provide insight into the molecular mechanisms underlying stretch-induced responses in rat ventricular myocytes, which may have implications for understanding cardiac physiology and pathophysiology.

Automated summary

This study identified specific ion channels and their potential role in regulating ionic currents in rat ventricular cardiomyocytes in response to mechanical stimulation. TRPM7, TRPC1, and TRPM4 channels were found to be mechanosensitive, while Ca(V)1.2 channels showed mechanosensitive properties. These findings provide insights into the molecular mechanisms underlying stretch-induced responses in rat ventricular myocytes and have implications for understanding cardiac physiology and pathophysiology.