カテコールアミンの頻拍作用に対するイオンコンダクタンスに影響する薬物の効果—抗頻拍作用

Influences of agents which affect ionic conductance on the tachycardiac effect of catecholamines:Antitachycardiac effect

　洞房結節細胞の歩調取り電位の成因は電気生理学的にはほぼ次のように考えられている。それは再分極に関係した主にK^＋により運ばれる電流I_Kの脱活性化と脱分極につれて次第に大きくなるCa電流の活性化がおもな成因とされ，過分極時に活性化される内向き電流（I_h，I_f）は歩調取り電位の土台としては重要であるが実際の成因としてはそれほど重要ではないとされている^1〜3）。カテコールアミンの電気生理学的作用としては上に述べた3電流をすべて増強することが知られているにもかかわらず^1），カテコールアミンの頻拍の成因としてこれらの3電流がどの程度寄与しているかに対しての研究はそれほど多く発表されてはいない^4）。そこで本研究においては種々のイオンコンダクタンスに影響する薬物の拍動数，isoproterenolにより生じた頻拍，そしてisoproterenolの用量—反応曲線に対する効果についてモルモット右心房標本を用いて検討した。

The influences of agents that affect ionic conductance on the atrial rates and the concentration-response curves for the positive chronotropic effect of isoproterenol were examined in guinea-pig right atria. Bay k 8644, a Ca-agonist, which increases the slow inward current (I_si) produced a positive chronotropic effect, the maximum of which was about half that produced by isoproterenol. In the presence of 10^-6 M Bay k 8644, the concentra-tion-response curves for isoproterenol were shifted up-ward without changing the pD₂ values for isoproterenol. Tetraethylammonium (TEA), BaCl₂, and CsCl which decrease potassium conductance (g_K) reduced both the basal rate and an increase in the rate induced by isopro-terenol. In the presence of 10^-3 M BaCl₂, the concent-ration-response curves for isoproterenol were shifed downward without changing the pD₂ values for isopro-terenol. In the presence of 10^-3-10^-2 M CsCl, the concentration-response curves for isoproterenol were shifted downward and to the right, i.e., pD₂ values for isoproterenol were decreased by CsCl dose-dependently. CsCl is also known to reduce hyperpolarization-activat-ing current (I_h). Thus, these results indicate that the increases in I_si, g_K and I_h are involved ionically in the positive chronotropic effect of isoproterenol. In the presence of TEA, BaCl₂+Bay k 8644, and CsCl+Bay k 8644, the baseline rates were almost the same as control untreated atrial rates, however the increases in rate induced by higher concentration of isoproterenol were reduced to the great extent. The antitachycardiac effect, which we coined "anti-" that means againt with "tachycardia" which means increased heart rate, was able to poduce by the simultaneous administration of Bay k 8644 which increases I_Casepecifically and agents which reduce g_K.