Recruitment of the intracellular Ca2+ by ultrashort electric stimuli: The impact of pulse duration

Nanosecond-duration electric stimuli are distinguished by the ability to permeabilize intracellular membranes and recruit Ca2+ from intracellular stores. We quantified this effect in non-excitable cells (CHO) using ratiometric Ca2+ imaging with Fura-2. In a Ca2+-free medium, 10-, 60-, and 300-ns stimuli evoked Ca2+ transients by mobilization of Ca2+ from the endoplasmic reticulum. With 2 mM external Ca2+, the transients included both extra- and intracellular components. The recruitment of intracellular Ca2+ increased as the stimulus duration decreased. At the threshold of 200-300 nM, the transients were amplified by calcium-induced calcium release. We conclude that nanosecond stimuli mimic Ca2+ signaling while bypassing the usual receptor- and channels-mediated cascades. The recruitment of the intracellular Ca2+ can be controlled by the duration of the stimulus.