Silva Jonathan, Rudy Yoram
Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, Cleveland, Ohio 44106-7207, USA.
Circ Res. 2003 Feb 21;92(3):261-3. doi: 10.1161/01.res.0000057996.20414.c6.
Biological pacemakers were recently created by genetic suppression of inward rectifier potassium current, I(K1), in guinea pig ventricular cells. We simulated these cells by adjusting I(K1) conductance in the Luo-Rudy model of the guinea pig ventricular myocyte. After 81% I(K1) suppression, the simulated cell reached steady state with pacemaker period of 594 ms. Pacemaking current is carried by the Na+-Ca2+ exchanger, I(NaCa), which depends on the intracellular calcium concentration [Ca2+]i. This [Ca2+]i dependence suggests responsiveness (increase in rate) to beta-adrenergic stimulation (betaAS), as observed experimentally. Simulations of betaAS demonstrate such responsiveness, which depends on I(NaCa) expression. However, a simultaneous betaAS-mediated increase in the slow delayed rectifier, I(Ks), limits betaAS sensitivity.
生物起搏器最近通过基因抑制豚鼠心室细胞中的内向整流钾电流I(K1)而产生。我们通过在豚鼠心室肌细胞的Luo-Rudy模型中调节I(K1)电导来模拟这些细胞。在抑制81%的I(K1)后，模拟细胞达到稳定状态，起搏周期为594毫秒。起搏电流由钠钙交换体I(NaCa)携带，其依赖于细胞内钙浓度[Ca2+]i。这种对[Ca2+]i的依赖性表明对β-肾上腺素能刺激（betaAS）有反应性（速率增加），这在实验中已观察到。对betaAS的模拟证明了这种反应性，其依赖于I(NaCa)的表达。然而，β-肾上腺素能刺激同时介导的缓慢延迟整流器I(Ks)的增加限制了β-肾上腺素能刺激的敏感性。
