Cardiac cell action potential duration is dependent upon induced changes in free Ca 2+ activity during pH changes in vitro

Abstract

We examined how changes in solution pH alter myocardial cell action potentials (AP) with and without changes in free [Ca2+] caused by pH induced effects on calcium binding. Guinea pig ventricular tissue was isolated, superfused either with Krebs-Ringer (K-R) bicarbonate, phosphate buffered solution, or with Hepes buffered solution, and electrically paced during control (5% CO2 in O2), acidic (12% CO2), and alkalotic (0% CO2) conditions. Action potentials were recorded with intracellular microelectrodes. Extracellular free [Ca2+] was measured with a calcium ion selective electrode and total soluble calcium was measured by ultrafiltration and spectrophotometry. With a total [CaCl2] of 2.5 mM in the K-R solution, we found a free [Ca2+] of 2.14 mM at pH 7.44 (control), 2.48 mM at pH 6.97 and 1.60 mM at pH 8.19; total soluble calcium concentration was 2.00 mM at pH 8.19. In the Hepes solution, free [Ca2+] was only slightly altered (2.42 to 2.55 mM) within this pH range. Equivalent acidosis of either K-R or Hepes suffusate significantly, and similarly, prolonged the AP and its refractory period. Alkalosis of the Hepes suffusate shortened the AP; but equivalent alkalosis of the K-R suffusate prolonged the AP as did a reduction of [CaCl2] in Hepes suffusate from 3.0 to 1.5 mM at pH 7.43. Our study demonstrates that a paradoxical increase in APD occurs because free Ca2+ ion activity falls in K-R solution and overrides the effect of alkalosis alone to decrease APD.(ABSTRACT TRUNCATED AT 250 WORDS)