Proton conductance of human transient receptor potential-vanilloid type-1 expressed in oocytes of Xenopus laevis and in Chinese hamster ovary cells.

Transient receptor potential-vanilloid type-1 (TRPV1) is a ligand-gated cation channel with preference for divalent cations, especially Ca(2+) (sequence of conductances: Ca(2+)>Mg(2+)>Na(+) approximately/= K(+) approximately/= Cs(+)). In the present study, the two-electrode voltage-clamp technique was used on oocytes of Xenopus laevis expressing TRPV1 to evaluate whether human TRPV1 also conducts protons. In medium devoid of K(+), Na(+), Mg(2+), and Ca(2+), capsaicin 1 microM induced a significant inward current (62% of the current in physiological medium). The effects of capsaicin were abolished in the presence of capsazepine 3 microM. The capsaicin-induced currents in medium devoid of Na(+), K(+), Mg(2+), and Ca(2+) were dependent on pH, causing larger inward currents and less negative reversal potentials at low pH and vice versa. The same current was also demonstrated in Chinese hamster ovary cells expressing human TRPV1. We conclude that TRPV1 conducts protons, in addition to Na(+), K(+), Mg(2+), and Ca(2+). The proton conductance may help to initiate action potentials and to translocate H(+) dependent on TRPV1 activation and membrane potential.

Differences in the nitric oxide/soluble guanylyl cyclase signalling pathway in the myocardium of neonatal and adult rats.

The effects of a nitric oxide-donor, S-nitroso-N-acetylpenicillamine, and a direct activator of soluble guanylyl cyclase, 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), on force of contraction (F(c)) and L-type Ca(2+) currents (I(Ca(L))) were investigated in myocardial preparations from neonatal and adult rats. Since hearts from adult and neonatal animals contained 160 and 47 mg/100 g wet weight myoglobin, respectively, its possible interaction with both drugs was also investigated. Both S-nitroso-N-acetylpenicillamine (100 microM) and YC-1 (30 microM) were ineffective in myocardial preparations from adult rats but reduced the magnitude of I(Ca(L)) and F(c) in preparations from neonatal rats. The latter effects were antagonised by 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 microM) and attenuated by myoglobin (30-300 microM), which also attenuated the effects of both drugs on pre-contracted aortic rings. The differential effects of S-nitroso-N-acetylpenicillamine and YC-1 in the myocardium from adult and neonatal rats may result from developmental changes in the content of myoglobin and/or in the NO/soluble guanylyl cyclase signal pathway.