Spatial heterogeneity of transmembrane potential responses of single guinea-pig cardiac cells during electric field stimulation.

Changes in transmembrane voltage (V(m)) of cardiac cells during electric field stimulation have a complex spatial- and time-dependent behaviour that differs significantly from electrical stimulation of space-clamped membranes by current pulses. A multisite optical mapping system was used to obtain 17 or 25 microm resolution maps of V(m) along the long axis of guinea-pig ventricular cells (n = 57) stained with voltage-sensitive dye (di-8-ANEPPS) and stimulated longitudinally with uniform electric field (2, 5 or 10 ms, 3-62 V cm(-1)) pulses (n = 201). The initial polarizations of V(m) responses (V(mr)) varied linearly along the cell length and reversed symmetrically upon field reversal. The remainder of the V(m) responses had parallel time courses among the recording sites, revealing a common time-varying signal component (V(ms)). V(ms) was depolarizing for pulses during rest and hyperpolarizing for pulses during the early plateau phase. V(ms) varied in amplitude and time course with increasing pulse amplitude. Four types of plateau response were observed, with transition points between the different responses occurring when the maximum polarization at the ends of the cell reached values estimated as 60, 110 and 220 mV. Among the cells that had a polarization change of > 200 mV at their ends (for fields > 45 V cm(-1)), some (n = 17/25) had non-parallel time courses among V(m) recordings of the various sites. This implied development of an intracellular field (E(i)) that was found to increase exponentially with time (tau = 7.2 +/- 3.2 ms). Theoretical considerations suggest that V(ms) represents the intracellular potential (phi(i)) as well as the average polarization of the cell, and that V(mr) is the manifestation of the extracellular potential gradient resulting from the field stimulus. For cells undergoing field stimulation, phi(i) acts as the cellular physiological state variable and substitutes for V(m), which is the customary variable for space-clamped membranes.