title: Extracellular proton depression of peak and late Na⁺ current in the canine left ventricle.
abstract: 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.
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York 13501, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Murphy
authors.forename: Danielle
authors.initials: D
authors.lastname: Renodin
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
authors.forename: José M
authors.initials: JM
authors.lastname: Di Diego
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cordeiro
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D004699:Endocardium / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium