Effects of caffeine on the excitability and intracellular Ca(2+) transients of neonatal rat hypoglossal motoneurons in vitro.
Since constitutively-high intracellular Ca(2+) ([Ca(2+)](i)) may confer hypoglossal motoneurons special vulnerability to excitoxic damage, we investigated the spatiotemporal dynamics of [Ca(2+)](i) and its relation to spike firing of rat hypoglossal motoneurons recorded under whole-cell patch clamp coupled with high resolution [Ca(2+)](i) imaging. A rise in [Ca(2+)](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 [Ca(2+)](i) stores by caffeine increased background [Ca(2+)](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 [Ca(2+)](i) transients was more than doubled by caffeine, although peak [Ca(2+)](i) remained unchanged. It is suggested that the main role of caffeine-sensitive stores was to buffer [Ca(2+)](i) elevated by sustained firing and to control spike accommodation.
Donato
Roberta
R
Biophysics Sector and INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 4, 34014, Trieste, Italy.
Canepari
Marco
M
Lape
Remigijus
R
Nistri
Andrea
A
D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D005456:Fluorescent Dyes; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009930:Organic Chemicals; D018408:Patch-Clamp Techniques; D051381:Rats
D005456:Fluorescent Dyes; C403124:Oregon Green BAPTA-dextran; D009930:Organic Chemicals; D002110:Caffeine; D002118:Calcium