抄録
It has been reported that myocardial ischemia and angiotensin-I converting enzyme inhibition therapy are associated with increased bradykinin level in cardiac tissues. Bradykinin modulates the inotropic and chronotropic cardiac function, and these actions are believed to be mediated via central nervous system reflexes. Although the heart is innervated by parasympathetic and sympathetic nervous system, an extensive neural network exists in the heart. In addition, bradykinin is suggested to exert negative chronotropic effect via intrinsic cardiac neurons. However, the effect of bradykinin on intrinsic cardiac neurons remains to be clarified. In the present study, therefore, we investigated the effect of bradykinin on the intracardiac ganglion neurons acutely isolated from rats using patch-clamp recording technique.
Under current-clamp conditions with an amphotericin-B perforated-patch recording mode, application of 0.1 microM bradykinin depolarized the membrane, accompanied by repetitive firing of action potentials. The bradykinin action was fully inhibited by the B2 receptor antagonist HOE-140, but not by the B1 receptor antagonist Des-Arg9-[Leu8]-bradykinin. Bradykinin evoked inward currents under voltage-clamp conditions at a holding potential of -60 mV. Removal of extracellular Ca2+ markedly increased the bradykinin-induced currents, suggesting an involvement of non-selective cation channels. Bradykinin also reduced the amplitude of M-current deactivation induced by a hyperpolarizing step from a holding potential of -20 mV to -60 mV.
From these results we suggest that bradykinin excites the intrinsic cardiac neurons associated with both an activation of non-selective cation channels and an inhibition of M-type K+ channels through the B2 type of bradykinin receptors.
This study was supported by KAKENHI (15H03046 & 16K13050)
