Effects of caffeine on the excitability and intracellular Ca2+ transients of neonatal rat hypoglossal motoneurons in vitro

Since constitutively-high intracellular Ca2+ ([Ca2+](i)) may confer hypoglossal motoneurons special vulnerability to excitoxic damage, we investigated the spatiotemporal dynamics of [Ca2+](i) and its relation to spike firing of rat hypoglossal motoneurons recorded under whole-cell patch clamp coupled with high resolution [Ca2+](i) imaging. A rise in [Ca2+](i), appearing in conjunction with single action potentials and becoming larger during spike trains, was first detected immediately beneath the cell membrane area, peaked 10-20 ms after each spike, and propagated to the cell core with slow decay time. Depletion of ryanodine-sensitive [Ca2+](i) stores by caffeine increased background [Ca2+](i), augmented the spike medium afterhyperpolarization, slowed down the action potential firing rate and depolarized cells (after an early hyperpolarization). The decay time constant of [Ca2+](i) transients was more than doubled by caffeine, although peak [Ca2+](i) remained unchanged. It is suggested that the main role of caffeine-sensitive stores was to buffer [Ca2+](i) elevated by sustained firing and to control spike accommodation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.