Extracellular proton depression of peak and late Na+ current in the canine left ventricle

作者：Murphy Lisa; Renodin Danielle; Antzelevitch Charles; Di Diego Jose M; Cordeiro Jonathan M^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2011, 301(3): H936-H944.

DOI：10.1152/ajpheart.00204.2011

• sodium current
• acidosis
• ischemia
• epicardium
• endocardium

Murphy L, Renodin D, Antzelevitch C, Di Diego JM, Cordeiro JM. Extracellular proton depression of peak and late Na+ current in the canine left ventricle. Am J Physiol Heart Circ Physiol 301: H936-H944, 2011. First published June 17, 2011; doi:10.1152/ajpheart.00204.2011.-Cardiac ischemia reduces excitability in ventricular tissue. Acidosis (one component of ischemia) affects a number of ion currents. We examined the effects of extracellular acidosis (pH 6.6) on peak and late Na+ current (I-Na) in canine ventricular cells. Epicardial and endocardial myocytes were isolated, and patch-clamp techniques were used to record I-Na. Action potential recordings from left ventricular wedges exposed to acidic Tyrode solution showed a widening of the QRS complex, indicating slowing of transmural conduction. In myocytes, exposure to acidic conditions resulted in a 17.3 +/- 0.9% reduction in upstroke velocity. Analysis of fast I-Na showed that current density was similar in epicardial and endocardial cells at normal pH (68.1 +/- 7.0 vs. 63.2 +/- 7.1 pA/pF, respectively). Extracellular acidosis reduced the fast I-Na magnitude by 22.7% in epicardial cells and 23.1% in endocardial cells. In addition, a significant slowing of the decay (time constant) of fast I-Na was observed at pH 6.6. Acidosis did not affect steady-state inactivation of I-Na or recovery from inactivation. Analysis of late I-Na during a 500-ms pulse showed that the acidosis significantly reduced late I-Na at 250 and 500 ms into the pulse. Using action potential clamp techniques, application of an epicardial waveform resulted in a larger late I-Na compared with when an endocardial waveform was applied to the same cell. Acidosis caused a greater decrease in late I-Na when an epicardial waveform was applied. These results suggest acidosis reduces both peak and late I-Na in both cell types and contributes to the depression in cardiac excitability observed under ischemic conditions.

• 出版日期2011-9