ウサギ心室筋における過酸化水素誘発性L型Ca²⁺電流増大はPKCεアイソフォームを介して修飾される。

抄録

Hydrogen peroxide (H₂O₂) is produced during post ischemic reperfusion. It is reported that H₂O₂ increases L-type Ca²⁺ current (I_Ca,L), while catalase, a scavenger of H₂O₂, can alter response to β-stimulation of I_Ca,L. L-type Ca²⁺ channels (LCC) are mainly modified via cAMP/PKA pathway, however, it is not yet clear about the mechanisms of the effects of H₂O₂ on LCC. The purpose of the present study is to examine the mechanism that involved in H₂O₂-induced modification of LCC. We applied H₂O₂ to isolated rabbit ventricular myocytes and measured I_Ca,L by whole-cell patch clamp technique. We examined to H₂O₂-induced increase of I_Ca,L in the presence of a PKA activator, a PKA inhibitor and a non-selective PKC inhibitor (BIS). We also observed the effect of PKC inhibitor peptide specific to each subtypes through the pipette solution. In control group (CT), H₂O₂ increased I_Ca,L to 1.20±0.04 folds. Neither activation nor inhibition of PKA affected the H₂O₂-induced increase in I_Ca,L. In contract, BIS inhibited the H₂O₂-induced increase in I_Ca,L (0.80±0.07 folds). When non-selective PKC inhibitor peptide dialyzed intracellularly, H₂O₂-induced increase in I_Ca,L was suppressed (1.00±0.05 folds). PKCε inhibitor peptide, but not PKCδ inhibitor peptide dialyzed to pipette solution similarly inhibited the H₂O₂-induced increase in I_Ca,L(1.04±0.05 folds). These results suggest that modification of LCC by H₂O₂ is not through the PKA pathway, but through PKC, especially through PKCε pathway. [J Physiol Sci. 2007;57 Suppl:S229]