기니픽 심근의 수축력과 세포내 Na⁺ 활성도에 미치는 α₁-Adrenergic 수용체 자극효과

Effects ofα₁-Adrenergic Stimulation on Contractility and Intracellular Na⁺ Activity of Guinea Pig Ventricular Muscles

Myocardial α₁-Adrenoceptors have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an α₁-Adrenoceptors-induced intracellular Na⁺ decrease is linked to fast Na⁺ channel inhibition and another group reported that it is linked to Na⁺-K⁺ pump activation by α_1b-adrenoceptors. But until now, its mechanism is not clear. Therefore, to see whether the Na⁺channel or Na⁺-K⁺ pump is related to a decrease in intracellular Na⁺ activity and/or the negative inotropic response, and which α₁-Adrenoceptor subtype was involved in the decrease in intracellular Na⁺activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of α₁-adrenergic stimulation on membrane potential, intracellular Na⁺ activity, and twitch force in guinea pig ventricular muscles. 10^-5 M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in a_{Nⁱ_a}, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular Na⁺activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular Na⁺ activity. The decrease in intracellular Na⁺ activity was apparently inhibited by WB4101, an antagonist of the α_1a-adrenoceptors. The decrease in intracellular Na⁺ activity caused by phenylephrine was not abolished or reduced by a block of the fast Na⁺ channels. V_max also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular Na⁺ activity in the presence of a high concentration of extracellular Ca²⁺ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the α_1a-adrenoceptors-mediated decrease in intracellular Na⁺ activity may be related to the protein kinase C.