TY - JOUR T1 - Calcium-Induced Calcium Release Contributes to Action Potential-Evoked Calcium Transients in Hippocampal CA1 Pyramidal Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4325 LP - 4336 DO - 10.1523/JNEUROSCI.19-11-04325.1999 VL - 19 IS - 11 AU - Vladislav M. Sandler AU - Jean-Gaƫl Barbara Y1 - 1999/06/01 UR - http://www.jneurosci.org/content/19/11/4325.abstract N2 - 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. ER -