CALCIUM-INDUCED CALCIUM-RELEASE IN NEURONS

Neurones express several subtypes of intracellular Ca2+ channels, whic h are regulated by cytoplasmic calcium concentration ([Ca2+](c)) and p rovide the pathway for Ca2+-induced Ca2+ release (CICR) from endoplasm ic reticulum Ca2+ stores. The initial studies of CICR which employed s everal pharmacological tools (and in particular caffeine and ryanodine ) demonstrated that: (i) caffeine induces intracellular calcium releas e in various peripheral and central neurones; and (ii) inhibition of C ICR affects the parameters of depolarization-triggered [Ca2+](c) respo nses. Experiments with caffeine demonstrated also that Ca2+ release fr om internal pools was incremental, suggesting the coexistence of sever al subpopulations of Ca2+ release channels with different sensitivity to caffeine. The CICR availability in neurones is controlled by both t he Ca2+ content of the internal stores and the basal [Ca2+](c). Direct comparison of transmembrane Ca2+ influx with plasmalemmal Ca2+ curren t and [Ca2+](c) elevation performed on sympathetic, sensory and cerebe llar Purkinje neurones revealed the gradual activation of CICR. The ef ficacy of CICR may be regulated by the newly discovered second messeng er cADP ribose (cADPR), although the mechanism of signal transduction involving cADPR is still unknown. CICR in neurones may be important in creation of local [Ca2+](c) signals and could be involved in a regula tion of numerous neuronal functions.