The nature of the external ionic modulation of the myocardial electrical propagation: Importance of the safety factor

The mechanisms of conduction change depending on the extracellular K⁺ and Ca²⁺ concentrations ([K⁺](o) and [Ca²⁺](o), respectively) were investigated. Simultaneous measurements of active and passive membrane properties and net membrane excitability were fulfilled by arranging the intra- and extracellular microelectrodes in a superfused and paced guinea pig papillary muscle. Internal longitudinal resistance (r(i)), as a parameter of passive property, was evaluated by the intra- and extracellular voltage ratio. The maximum upstroke rate (V̇(max)) was used as an active property. Apparent threshold potential (V(th)) was defined by the breakpoint in the action potential upstroke fitted semilogarithmically. Graded rise in [K⁺](o) (from 2.7 to 15.0 mM) evoked a progressive fall in V̇(max), and was associated with less negative resting membrane potential and constant r(i). Conduction velocity (Θ) was the maximum in 9.0 mM [K⁺](o) ('supernormal' conduction) but not in 2.7 mM [K⁺](o) which gave the greatest V̇(max) ('subnormal' conduction). Safety factor of conduction (S), as an index of net excitability, could most readily account for the [K⁺](o)-dependent change in Θ. This was true also in the case of [Ca²⁺](o) elevation (from 0.9 to 5.4 mM). These results indicate that the cation-modulated propagation is governed by the cable theory including S as a matrix of combined active and passive properties.