title: Calcium-induced calcium release contributes to action potential-evoked calcium transients in hippocampal CA1 pyramidal neurons.
abstract: Calcium-induced calcium release (CICR) is a mechanism by which local elevations of intracellular calcium (Ca2+) are amplified by Ca2+ release from ryanodine-sensitive Ca2+ stores. CICR is known to be coupled to Ca2+ entry in skeletal muscle, cardiac muscle, and peripheral neurons, but no evidence suggests that such coupling occurs in central neurons during the firing of action potentials. Using fast Ca2+ imaging in CA1 neurons from hippocampal slices, we found evidence for CICR during action potential-evoked Ca2+ transients. A low concentration of caffeine enhanced Ca2+ transient amplitude, whereas a higher concentration reduced it. Simultaneous Ca2+ imaging and whole-cell recordings showed that membrane potential, action potential amplitude, and waveform were unchanged during caffeine application. The enhancement of Ca2+ transients by caffeine was not affected by the L-type channel blocker nifedipine, the phosphodiesterase inhibitor IBMX, the adenylyl cyclase activator forskolin, or the PKA antagonist H-89. However, thapsigargin or ryanodine, which both empty intracellular Ca2+ stores, occluded this effect. In addition, thapsigargin, ryanodine, and cyclopiazonic acid reduced action potential-evoked Ca2+ transients in the absence of caffeine. These results suggest that Ca2+ release from ryanodine-sensitive stores contributes to Ca2+ signals triggered by action potentials in CA1 neurons.
authors.affiliation: New York Medical College, Department of Physiology, Valhalla, New York 10595, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Sandler
authors.forename: J G
authors.initials: JG
authors.lastname: Barbara
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D055095:Optics and Photonics; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; C049925:fura-2-am; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium; D016257:Fura-2