CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
The electrogenic Na+/HCO3- cotransport contributes to the shaping of the cardiac action potential.
MARÍA C. VILLA-ABRILLE; MARTÍN G. VILA PETROFF; ERNESTO A. AIELLO
Congreso; American Heart Association Scientific Sessions 2006; 2006
American Heart Association
Electroneutral and electrogenic isoforms of the Na+/HCO3- cotransporter (NBC) co-exist in the myocardium. We have previously suggested that the electrogenic NBC (2 HCO3-:1 Na+) contributes to the modulation of the spike-like rat action potential (AP) waveform. However, the participation of this transporter in the configuration of the typical prolonged cardiac AP of larger mammals is an interesting issue that remains to be studied. Thus, perforated-patch was used to determine the contribution of the electrogenic NBC to the shaping of cardiac AP in cat ventricular myocytes. Switching from HEPES- to HCO3- (20 mmol/L)-buffered solution at constant extracellular pH (7.4) hyperpolarized resting membrane potential (RMP) by 2.7±0.4 mV (n=9, p<0.05). The AP duration (APD) measured at 50 % of repolarization time (APD50) was 35.8±6.8 % shorter in the presence of HCO3- than in its absence (n=9, p<0.05). The magnitude of the HCO3--induced APD shortening was dependent on the extracellular concentration of this ion (APD50 shortening in 5 mmol/L HCO3-: 19.3±4.6 %, n=9, p<0.05). The anionic blocker, SITS (0.1 mmol/L), reversed (Em; HEPES: -73.1±2.4 mV, HCO3-: -76.2±2.7 mV, p<0.05, and HCO3-+SITS: -73.5±2.8 mV; n=4) and prevented (Em; HEPES: -75.1±2.4 mV, HEPES+SITS: -75.8±0.7 mV, and HCO3-+SITS: -76.3±0.7 mV; n=4) the HCO3--induced RMP hyperpolarization. The HCO3--induced APD shortening was also reversed (APD50; HEPES: 540±50 ms, HCO3-: 350±40 ms, p<0.05, and HCO3-+SITS: 560±70 ms; n=4) and prevented (APD50; HEPES: 672±87 ms, HCO3-: 695±70 ms, and HCO3-+SITS: 670±42 ms; n=4) by SITS. In addition, no HCO3--induced RMP hyperpolarization and APD shortening was observed in the absence of extracellular Na+. Steady-state currents were evoked by 8 seconds duration voltage-clamped ramps ranging from -130 to +30 mV. A SITS-sensitive current was observed in the presence of HCO3-. The HCO3--sensitive current reversed at 87±5 mV (n=7), a value close to the expected reversal potential of an electrogenic NBC with a HCO3-:Na+ stoichiometry ratio of 2:1. We conclude that the anionic current carried by the electrogenic NBC has a relevant influence on RMP and APD, participating as a physiological contributor of ventricular repolarization.