Acidosis inhibits spontaneous activity and membrane currents in myocytes isolated from the rabbit atrioventricular node

作者：Cheng Hongwei; Smith Godfrey L; Orchard Clive H^*; Hancox Jules C

来源：Journal of Molecular and Cellular Cardiology, 2009, 46(1): 75-85.

DOI：10.1016/j.yjmcc.2008.09.709

• Acidosis
• Action potential
• Atrioventricular node
• AV node
• AVN
• L-type calcium current
• Pacemaking
• Rapid delayed rectifier current
• Single cell
• Spontaneous activity

Recent evidence from intact hearts suggests that the function of cardiac nodal tissue may be particularly susceptible to acidosis. Little is currently known, however, about the effects of acidosis on the cellular electrophysiology of the atrioventricular node (AVN). This study was conducted, therefore, to determine the effect of acidosis on the spontaneous activity and membrane currents of myocytes isolated from the rabbit AVN, recorded at 35-37 degrees C using whole-cell patch-clamp. Reduction of extracellular pH (pH(e); from 7.4 to 6.8 or 6.3) produced pH-dependent slowing of spontaneous action potential rate and upstroke velocity, and reductions in maximum diastolic potential and action potential amplitude. Ionic current recordings under voltage-clamp indicated that acidosis (pH(e) 6.3) decreased L-type Ca current (I-Ca,I-L), without significant changes in voltage-dependent activation or inactivation. Acidosis reduced the E-4031-sensitive, rapid delayed rectifier current (I-Kr) tail amplitude at -40 mV following command pulses to between -30 and 50 mV, and accelerated tail-current deactivation. In contrast, the time-dependent hyperpolarisation-activated current, If, was unaffected by acidosis. Background current insensitive to E-4031 and nifedipine was reduced by acidosis. Measurement of intracellular pH (pH(i)) from undialysed cells using BCECF showed a reduction in mean pHi from 7.24 to 6.45 (n = 17) when pH. was lowered from 7.4 to 6.3. We conclude that If is unlikely to be involved in the response of the AVN to acidosis, whilst inhibition of I-Ca.L and I-Kr by acidosis are likely to play a significant role in effects on AVN cellular electrophysiology.

• 出版日期2009-1