L-Type Calcium Channels Mediate Calcium Oscillations in Early Postnatal Purkinje Neurons

Abstract

Ca2ϩ signaling is important in many fundamental neuronal processes including neurotransmission, synaptic plasticity, neuronal development, and gene expression. In cerebellar Purkinje neurons, Ca 2ϩ signaling has been studied primarily in the dendritic region where increases in local Ca 2ϩ have been shown to occur with both synaptic events and spontaneous electrical activity involving P-type voltage-gated Ca 2ϩ channels (VGCCs), the predominant VGCC expressed by Purkinje neurons. Here we show that Ca 2ϩ signaling is also a prominent feature of immature Purkinje neurons at developmental stages that precede expression of dendritic structure and involves L-type rather than P-type VGCCs. Immature Purkinje neurons acutely dissociated from postnatal day 4-7 rat pups exhibit spontaneous cytoplasmic Ca 2ϩ oscillations. The Ca 2ϩ oscillations require entry of extracellular Ca 2ϩ , are blocked by tetrodotoxin, are communicated to the nucleus, and correlate closely with patterns of endogenously generated spontaneous and evoked electrical activity recorded in the neurons. Immunocytochemistry showed that L-, N-, and P/Q-types of VGCCs are present on the somata of the Purkinje neurons at this age. However, only the L-type VGCC antagonist nimodipine effectively antagonized the Ca 2ϩ oscillations; inhibitors of P/Q and N-type VGCCs were relatively ineffective.

Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

“…Such a store might release [Ca 2ϩ ] i via a IP 3 -mediated mechanism or via Ca 2ϩ -induced Ca 2ϩ release (CICR). Metabotropic glutamate receptor-mediated delayed Ca 2ϩ release is essential in PC dendrites and spines (Finch and Augustine, 1998;Takechi et al, 1998), but its putative role in shaping somatic Ca 2ϩ transients is less clear and may be of importance mainly during postnatal PC development (Liljelund et al, 2000;Nelson et al, 2004). We hypothesize that ER-mediated Ca 2ϩ oscillations (waves) are decreasing in parallel to the increase in PV expression also based on results that in oocytes, PV prevents the generation of IP 3 -induced Ca 2ϩ waves and restricts Ca 2ϩ signals to local Ca 2ϩ release sites (Dargan et al, 2004).…”

Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor

“…This finding raises the interesting hypothesis that the relative contribution of PP-2A and other phosphatases might change during cerebellar maturation, with PP-1-related phosphatase regulating synaptogenesis and plasticity at early developmental stages, whereas PP-2A would play a dominant role only at more mature stages. It should be noted that the period between the second and third postnatal week in vivo corresponds to an extensive synaptic remodeling (disappearance of functional N-methyl-Daspartate receptors and of multiple climbing fiber innervation) and changes in electrical properties resulting from alteration of voltage-dependent channel populations (45,46). The signaling cascade underlying cerebellar LTD also appears to undergo considerable maturation during this period, with neither IP 3 nor NO required in immature PCs (47,48), whereas these signals are necessary in the mature cerebellum (5).…”

Homeostasis established by coordination of subcellular compartment plasticity improves spike encoding

“…Axonal HFA probably activates voltage-gated Ca 2+ channels (Tsien et al, 1988;Fisher et al, 1990) and raises Ca 2+ in cells (Ehlers and Augustine, 1999;Liljelund et al, 2000 Fig. 9A; n=8, P=0.78), respectively.…”