O'Neill M, Ryan D M, Paterson D J
University Laboratory of Physiology, Oxford, UK.
Acta Physiol Scand. 1995 Jul;154(3):367-76. doi: 10.1111/j.1748-1716.1995.tb09920.x.
Modulation of the L-type calcium channel by catecholamines improves action potential parameters in single ventricular myocytes depolarized by high [K+]o Tyrode. Whether this modulation is important in offsetting the negative effects of hyperkalaemia in the whole heart is not known. We tested the effects of the calcium channel antagonist, verapamil, on restoration of cardiac performance by adrenergic stimulation in high [K+]o in anaesthetized rabbits and isolated perfused working rabbit hearts. Raised [K+]o decreased SBP, LVP and LVdP/dtmax in vivo ([K+]a 8.6 +/- 0.2 mM; n = 10) and aortic flow (AF) in the isolated heart (8 mM [K+]o Tyrode; n = 25). However, the negative effects of raised [K+]a were offset by isoprenaline (Iso, 1 microgram kg-1 min-1 i.v.) in vivo and by noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg-1 i.v.; 15 nM isolated heart) markedly potentiated the negative inotropic effects of raised [K+]o in both preparations. Verapamil attenuated the effect of isoprenaline in vivo but in the isolated heart, the protective effect of NA in 8 mM [K+] Tyrode (AF 97 +/- 10 mL min-1 in 8 mM [K+]o compared with AF 141 +/- 8.5 mL min-1 in 8 mM [K+]o + NA) was offset by the drug (90 +/- 8 mL min-1 in 8 mM [K+]o + NA + V). Furthermore, verapamil abolished aortic flow in 8 mM [K+]o alone. These findings suggest that the heart may be critically dependent on modulation of intracellular calcium in order to tolerate concentrations of K+ similar to those seen during a short burst of intensive exercise ([K+]a 8.6 mM).
儿茶酚胺对L型钙通道的调节作用可改善高[K⁺]ₒ Tyrode溶液去极化的单个心室肌细胞的动作电位参数。尚不清楚这种调节作用在抵消高钾血症对全心的负面影响方面是否重要。我们在麻醉兔和离体灌注的工作兔心脏中，测试了钙通道拮抗剂维拉帕米对高[K⁺]ₒ条件下肾上腺素能刺激恢复心脏功能的影响。升高的[K⁺]ₒ可降低体内的收缩压（SBP）、左心室压（LVP）和左心室dp/dtmax（[K⁺]ₐ 8.6±0.2 mM；n = 10）以及离体心脏中的主动脉流量（AF）（8 mM [K⁺]ₒ Tyrode溶液；n = 25）。然而，升高的[K⁺]ₐ的负面影响在体内被异丙肾上腺素（Iso，1 μg kg⁻¹ min⁻¹静脉注射）抵消，在离体心脏中被去甲肾上腺素（NA，80 nM）抵消。维拉帕米（0.15 mg kg⁻¹静脉注射；离体心脏中为15 nM）在两种制剂中均显著增强了升高的[K⁺]ₒ的负性肌力作用。维拉帕米减弱了体内异丙肾上腺素的作用，但在离体心脏中，NA在8 mM [K⁺] Tyrode溶液中的保护作用（8 mM [K⁺]ₒ时AF为97±10 mL min⁻¹，而8 mM [K⁺]ₒ + NA时AF为141±8.5 mL min⁻¹）被该药物抵消（8 mM [K⁺]ₒ + NA + V时为90±8 mL min⁻¹）。此外，维拉帕米单独在8 mM [K⁺]ₒ时可消除主动脉流量。这些发现表明，心脏可能严重依赖细胞内钙的调节，以便耐受类似于短时间剧烈运动期间所见的钾浓度（[K⁺]ₐ 8.6 mM）。
