Diffusion and electrogenic components of the resting potential in explanted neonatal rat ventricle cells

Spontaneously beating explanted neonatal rat ventricle cells stop beating and show a steady potential (the mean resting potential, -46.2 mV at 6.0 mM Ko) when exposed to 10 mM Cao or 4 mM Mn. When Ko was increased, resting potential changed only slightly between 3 and 15 mM, but the resting potential versus Ko characteristically approached the slope of a K electrode at high Ko. Elimination of Cl from the medium did not alter the K dependence of the resting potential. However, a hyperpolarization of 9 mV per 10-fold change was observed when Nao was decreased from 50 to 4 mM. Ouabain (10(-4) M) depolarized the membrane within 2 min to a stable level of about -30 mV in spontaneously beating cells and in those treated with Ca channel blockers. This potential was considered as the diffusion component of the membrane potential, Vdiff. Consequently the difference between resting potential and Vdiff represents the ouabain-sensitive or the electrogenic component of the resting potential. Using linearized versions of the Mullins and Noda as well as the Goldman - Hodgkin - Katz equations, we calculated that a PNa/PK between 0.25 and 0.35, a Na/K exchange ratio of 2.0, and a Ki of 160 mM adequately described the K dependence of the resting potential. We demonstrated the contribution of electrogenic Na extrusion to the resting potential of mammalian cardiac cells in culture. Therefore the existence of a composite resting potential precludes the direct comparison of potential measurements obtained under conditions liable to independently modify either the diffusion or the electrogenic component.