Frequency-dependent excitability enhancement in isolated ventricular myocardial cells

The understanding of the mechanisms underlying the frequency-dependent slow response excitability enhancement has been hindered by the problems inherent in multicellular preparations. These include ion accumulation/depletion in intercellular spaces and difficulties in the spatial control of transmembrane voltage. In the present communication we show that isolated ventricular cells exposed to a depolarizing (high potassium-barium containing) solution present electrophysiological properties similar to those of multicellular preparations: stable resting potential of -45.2 +/- 0.7 mV (mean +/- SEM, N = 57) in 75% of the cells and spontaneous activity in the remaining 25% (maximum diastolic potential of -41.9 +/- 1.2 mV, N = 19); high input resistance and slow response, under current clamp conditions. Under whole cell voltage clamp conditions with -45 mV holding potential, transient outward and delayed potassium currents as well as typical L type calcium channel are present. These cells also present the frequency-dependent excitability enhancement of the slow response, with the threshold stimulus at 1 Hz corresponding to about 50% of that obtained at 0.1 Hz. Thus, isolated ventricular cells constitute a suitable model for the study of frequency-dependent excitability enhancement of the slow response.