Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes

Aims Hydrogen sulphide (H2S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H2S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H2S is a novel inhibitor of the L-type calcium channel current (I-Ca,I-L). Methods and results Electrophysiological measurements were performed in cardiomyocytes isolated from Wistar-Kyoto and spontaneously hypertensive rats. Bath application of 100 mu M NaHS (a H2S donor) significantly reduced the time required for the repolarization of the action potential. Inhibition of the peak I-Ca,I-L by NaHS was determined to be concentration-dependent (25, 50, 100, 200, and 400 mu M). NaHS inhibited the recovery from depolarization-induced inactivation. Electric field-induced [Ca2+]i transients and contraction of single cardiomyocytes and isolated papillary muscles were reduced by NaHS treatment. In contrast, caffeine induced an increase in [Ca2+]i that was riot altered by NaHS. NaHS had no effect on the K-ATP current or on the levels of cAMP and cGMP in the current study. Conclusion H2S is a novel inhibitor of L-type calcium channels in cardionnyocytes. Moreover, H2S-induced inhibition of [Ca2+] i appears to be a secondary effect owing to its initial action towards I-Ca,I-L. The inhibitory effect of H2S on I-Ca,I-L requires further investigation, particularly in the exploration of new pathways involved in cardiac calcium homeostasis and disease pathology.