P-type calcium channels in the somata and dendrites of adult cerebellar purkinje cells

Usowicz, Maria M.; Sugimori, Mutsuyuki; Cherksey, Bruce D.; Llinás, Rodolfó R.

doi:10.1016/0896-6273(92)90076-p

Cited by 296 publications

(222 citation statements)

References 60 publications

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“…We previously analyzed mice lacking Ca v 2.1 (24), a pore-forming component of the P/Q-type VDCC (global Ca v 2.1 KO mice), and reported that Ca v 2.1 KO mice have persistent multiple-CF innervation in young adult PCs (25). Although the P/Q-type VDCC is a major high-threshold Ca 2+ channel in PCs (23), it is also a major VDCC in presynaptic terminals that mediates transmitter release in most of the central synapses including the cerebellum (26,27). To clarify the extent of contribution of postsynaptic P/Q-type VDCCs to developmental rearrangements of CF synapses, we generated PC-selective Ca v 2.1 knockout mice by using the Cre/ loxP recombination system and the C57BL/6 ES cell line RENKA (28,29).…”

Section: Resultsmentioning

confidence: 99%

“…Whereas several factors crucial for the late phase of CF synapse elimination have been disclosed (13)(14)(15)(16)(17)(18)(19)(20), mechanisms of biased strengthening of single CFs and the early phase of CF synapse elimination are unknown. Because synapse refinement critically depends on neuronal activity (1,4,5,16,21,22), we studied whether the P/Q-type voltage-dependent Ca 2+ channel (VDCC), the major high-threshold VDCC in PCs (23), is involved in the development of CF to PC synapses.…”

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confidence: 99%

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Postsynaptic P/Q-type Ca ²⁺ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

Hashimoto

Teräs

Miyazaki

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

104

117

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Neural circuits are initially redundant but rearranged through activity-dependent synapse elimination during postnatal development. This process is crucial for shaping mature neural circuits and for proper brain function. At birth, Purkinje cells (PCs) in the cerebellum are innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During postnatal development, a single CF is selectively strengthened in each PC through synaptic competition, the strengthened single CF undergoes translocation to a PC dendrite, and massive elimination of redundant CF synapses follows. To investigate the cellular mechanisms of this activity-dependent synaptic refinement, we generated mice with PC-selective deletion of the Ca v 2.1 P/Q-type Ca 2+ channel, the major voltage-dependent Ca 2+ channel in PCs. In the PC-selective Ca v 2.1 knockout mice, Ca 2+ transients induced by spontaneous CF inputs are markedly reduced in PCs in vivo. Not a single but multiple CFs were equally strengthened in each PC from postnatal day 5 (P5) to P8, multiple CFs underwent translocation to PC dendrites, and subsequent synapse elimination until around P12 was severely impaired. Thus, P/Q-type Ca 2+ channels in postsynaptic PCs mediate synaptic competition among multiple CFs and trigger synapse elimination in developing cerebellum.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Postsynaptic P/Q-type Ca ²⁺ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

Hashimoto

Teräs

Miyazaki

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

104

117

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“…In other preparations, for example, cultured hippocampal neurons, baclofen also weakly modulates an w-CgTX-insensitive current (Scholtz and Miller,199 1). In acutely isolated postnatal rat spinal cord neurons, baclofen not only inhibits both an N-type and a P-type Ca*+ current (Usowicz, 1992) but also has actions on a further highthreshold Ca*+ current that is resistant to blockers of N-, P-, and L-type Ca*+ channels (Mintz and Bean, 1993).…”

Section: Discussionmentioning

confidence: 99%

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

Wall

Dale

1994

J. Neurosci.

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Activation of GABAB receptors in the Xenopus embryo, a simple vertebrate, causes presynaptic inhibition of transmitter release from glycinergic spinal neurons and an increase in action potential threshold. To investigate the underlying mechanisms of GABAB receptor action, we have made whole-cell voltage-clamp recordings from acutely isolated Xenopus embryo spinal neurons. The GABAB receptor agonist baclofen caused a reversible reduction in the amplitude of Ca2+ currents. This reduction of Ca2+ currents appeared to be voltage dependent as it was removed at very positive potentials. Since the specific GABAB antagonists CGP35348, phaclofen, and 2-hydroxysaclofen all blocked the reduction in Ca2+ currents, we concluded that the modulation of the Ca2+ current was mediated by GABAB receptors. We have investigated the pharmacological identity of the Ca2+ current modulated by baclofen using the selective blocker omega-conotoxin, fraction GVIA (omega-CgTX). omega-CgTX selectively blocked voltage-gated Ca2+ currents without affecting the voltage-gated Na+ current. omega-CgTX substantially occluded the action of baclofen, suggesting that GABAB receptors modulate an omega-CgTX-sensitive Ca2+ current. Since GABAB receptors mediate presynaptic inhibition, we have studied the involvement of the omega-CgTX-sensitive Ca2+ current in synaptic transmission in the intact spinal cord. Inhibitory interneuron axons were stimulated to evoke monosynaptic IPSPs in motoneurons, and recorded intracellularly. Since omega-CgTX blocked inhibitory transmission, we concluded that the omega-CgTX-sensitive Ca2+ current plays an essential role in transmitter release. If modulation of this current were to occur in nerve terminals, it could contribute to the GABAB receptor-mediated presynaptic inhibition of transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Indeed, evidence exists for large functional and pharmacological diversity of native Cav2.1 channels (Mermelstein et al 1999, Randall and Tsien 1995, Tottene et al 1996, Tringham et al 2007, Usowicz et al 1992. They play a prominent role in initiating action-potential-evoked neurotransmitter release both at peripheral neuromuscular junctions and central synapses, mainly within the cerebellum, brainstem, and cerebral cortex (Katz et al 1996, Catterall 1998, Iwasaki et al 2000.…”

Section: C1 Cav21 (P/q-type) Calcium Channelsmentioning

confidence: 99%

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

Uchitel

Inchauspe

Urbano

et al. 2012

Journal of Physiology-Paris

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P-type calcium channels in the somata and dendrites of adult cerebellar purkinje cells

Cited by 296 publications

References 60 publications

Postsynaptic P/Q-type Ca ²⁺ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

Postsynaptic P/Q-type Ca ²⁺ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

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P-type calcium channels in the somata and dendrites of adult cerebellar purkinje cells

Cited by 296 publications

References 60 publications

Postsynaptic P/Q-type Ca 2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

Postsynaptic P/Q-type Ca 2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

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Postsynaptic P/Q-type Ca ²⁺ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

Postsynaptic P/Q-type Ca ²⁺ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum