Key result
Barium induces automaticity in nonpacemaker cells by decreasing potassium conductance, whereas elevated potassium suppresses it.
Demonstrates that ionic conductance, specifically potassium conductance (gK), is the primary determinant of whether a cardiac cell functions as a pacemaker.
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Potassium conductance determines pacemaker phenotype in cardiac cells; extends mechanistic insights but leaves open in vivo and clinical relevance.
Trypsin-dispersed cells from hearts (ventricles) of 7 to 8 day chick embryos were cultured 3 to 21 days. The cells became attached to the culture dish and assembled into monolayer communities. By means of a bridge circuit, one microelectrode was used for simultaneously passing current and recording membrane potentials (V(m)). The input resistance, calculated by the measured DeltaV(m) for a known step of current, averaged 10 M ohm. Electrotonic depolarization of nonpacemaker cells had no effect on frequency of firing. Within 2 min after addition of Ba(++) (5 to 10 mM) to the Tyrode bath, the cells became partially depolarized and quiescent nonpacemaker cells developed oscillations in V(m) which led to action potentials. With time, the depolarization became nearly complete and the input resistance increased 2 to 10 times. During such sustained depolarizations, action potentials were no longer produced and often tiny oscillations were observed; however, large action potentials developed during hyperpolarizing pulses. Thus, the automaticity of the depolarized cell became apparent during artificial repolarization. Sr(++) (5 to 10 mM) initially produced hyperpolarization and induced automaticity in quiescent nonpacemaker cells. Elevated [K(+)](o) (20 to 30 mM) suppressed automaticity of pacemaker cells and decreased R(m) concomitantly. Thus, Ba(++) probably converts nonpacemaker cells into pacemaker cells independently of its depolarizing action. Ba(++) may induce automaticity and depolarization by decreasing g(K), and elevated [K(+)](o) may depress automaticity by increasing g(K). The data support the hypothesis that the level of g(K) determines whether a cell shall function as a pacemaker.
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Sperelakis et al. (1966) studied Cultured chick embryo heart cells. Barium (Ba++) and Strontium (Sr++) vs. Normal Tyrode's solution was evaluated on Membrane potential, input resistance, and automaticity. Barium converted nonpacemaker cells into pacemaker cells by decreasing potassium conductance, while elevated potassium depressed automaticity.
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