Evidence for roles of the activating function in electric stimulation

The hypothesis that the activating function drives transmembrane voltage changes (ΔV _m) has been tested in hearts. Optical ΔV _m were measured during activating functions produced with nonuniform and uniform transparent electrodes. When a nonuniform electrode was used to produce ∂ ²V _e/∂x ², the signs of ΔV _m and ∂ ²V _e/∂x ² matched. The extracellular voltage gradients, often assumed important, did not predict ΔV _m. When a uniform electrode was used to eliminate ∂ ²V _e/∂x ², the signs of ΔV _m matched the signs of (∂g _i/∂x)(∂V _e/∂x) estimated from variations in heart width. Demonstration of the activating function as a determinant of stimulation may improve research and therapy that use electric stimulation.