Structure and functional expression of α1, α2, and β subunits of a novel human neuronal calcium channel subtype

Williams, Mark E.; Feldman, Daniel H.; McCue, Ann F.; Brenner, Robert; Veliçelebi, Gönül; Ellis, Steven B.; Harpold, Michael M.

doi:10.1016/0896-6273(92)90109-q

Cited by 494 publications

(316 citation statements)

References 39 publications

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“…While the irreversibly blocked component may correspond to the N type Ca*+ current, the identity of the reversibly blocked current is not clear. In some neurons there is evidence that w-CgTX will transiently block L-type currents (Tsien et al, 1988;Aosaki and Kasai, 1989;Williams et al, 1992b). However, it seems unlikely that w-CgTX is blocking an L-type current in our experiments because, like cultured Xenopus neurons (Barish,199 l), acutely isolated Xenopus neurons either do not possess or only have a very small dihydropyridinesensitive Ca*+ current (N. Dale, unpublished observation).…”

Section: Discussionmentioning

confidence: 78%

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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Section: Discussionmentioning

confidence: 78%

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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“…Although the immunohistochemical data support the presence of Ca V 1.3 channels on dendritic membranes (Carlin et al, 2000b), this is based on the presence of the α 1 1.3 subunit. The voltage of activation of the channels will depend also on the β and α 2 δ subunits (Williams et al, 1992;Tomlinson et al, 1993), neither of which have yet been identified and classified in motoneurons. Therefore, caution should be exercised in attributing specific biophysical properties to these channels.…”

Section: The Role Of Motoneuron Dendrites In Repetitive Firingmentioning

confidence: 99%

Beginning at the end: Repetitive firing properties in the final common pathway

Brownstone

2006

Progress in Neurobiology

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Since the early 20th century, it has been recognized that motoneurons must fire repetitive trains of action potentials to produce muscle contraction. In 1932, Sir John Eccles, together with Hebbel Hoff, found that action potential spike trains in motor axons were produced by "rhythmic centres", which were within the motoneurons themselves. Two decades later, Eccles attended a Cold Spring Harbor Symposium in NY, USA entitled "The Neuron". Two of the many notable presentations at this symposium were juxtaposed: one by Eccles from the University of Otago, Dunedin, NZL, and the other by J. Walter Woodbury and Harry Patton from the University of Washington, Seattle, USA. Both presentations included data obtained using sharp microelectrodes to study the intracellularly recorded potentials of cat motoneurons. In this review, I discuss some of the events leading up to and surrounding this jointly accomplished advance and proceed to discussion of subsequent studies over 5+ decades that have made use of intracellular recordings from motoneurons to study their repetitive firing behavior. This begins with early descriptions of primary and secondary range firing, and continues to the discovery of dendritic persistent inward currents and their relation to plateau potentials, synaptic amplification, and motoneuronal firing. Following a brief description of the possible mechanisms underlying spike frequency adaptation, I discuss the modulation of repetitive firing properties during various motor behaviors. It has become increasingly clear that the central nervous system has exquisite control of the repetitive firing of motoneurons. Eccles' work laid the foundation for the present-day study of these processes.

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“…cDNA of the third gene (CaCh3) was isolated from neural and endocrine tissues and represents a neuroendocrinespecific L-type calcium channel (Williams et al 1992a, Seino et al 1992, whereas the gene products of the fourth and fifth genes (CaCh4 and CaCh5) have been found exclusively in neural tissues. Calcium channels transiently expressed from cRNA of CaCh4 induce high-voltage-activated calcium currents that are insensitive to nifedipine and o-conotoxin but are inhibited by a mixture of toxins from the funnel web spider that characterize this channel as a P-type calcium channel (Mori et al 1991).…”

Section: The a Subunitmentioning

confidence: 99%

“…Two identical C@ cDNAs have been isolated from rabbit skeletal muscle and human brain (Williams et al 1992a), whereas the a,/6 cDNA isolated from rat brain (Rim et al 1992) predicts an identical 8 protein and a splice variant of the processed az protein.…”

Section: The A/6 Subunitmentioning

confidence: 99%