title: Hydrogen sulfide inhibits L-type calcium currents depending upon the protein sulfhydryl state in rat cardiomyocytes.
abstract: Hydrogen sulfide (H(2)S) is a novel gasotransmitter that inhibits L-type calcium currents (I (Ca, L)). However, the underlying molecular mechanisms are unclear. In particular, the targeting site in the L-type calcium channel where H(2)S functions remains unknown. The study was designed to investigate if the sulfhydryl group could be the possible targeting site in the L-type calcium channel in rat cardiomyocytes. Cardiac function was measured in isolated perfused rat hearts. The L-type calcium currents were recorded by using a whole cell voltage clamp technique on the isolated cardiomyocytes. The L-type calcium channel containing free sulfhydryl groups in H9C2 cells were measured by using Western blot. The results showed that sodium hydrosulfide (NaHS, an H(2)S donor) produced a negative inotropic effect on cardiac function, which could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM). H(2)S donor inhibited the peak amplitude of I( Ca, L) in a concentration-dependent manner. However, dithiothreitol (DTT), a reducing sulfhydryl modifier markedly reversed the H(2)S donor-induced inhibition of I (Ca, L) in cardiomyocytes. In contrast, in the presence of DM, H(2)S donor could not alter cardiac function and L type calcium currents. After the isolated rat heart or the cardiomyocytes were treated with DTT, NaHS could markedly alter cardiac function and L-type calcium currents in cardiomyocytes. Furthermore, NaHS could decrease the functional free sulfhydryl group in the L-type Ca(2+) channel, which could be reversed by thiol reductant, either DTT or reduced glutathione. Therefore, our results suggest that H(2)S might inhibit L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
authors.forename: Rongyuan
authors.initials: R
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Haojan
authors.initials: H
authors.lastname: Tsai
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002460:Cell Line; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000393:Air Pollutants; D020746:Calcium Channels, L-Type; D002118:Calcium; D006862:Hydrogen Sulfide