Omega-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle.

McCleskey, Edwin W.; Fox, Aaron P.; Feldman, Daniel H.; Cruz, L J; Olivera, B.M.; Tsien, Richard W.; Yoshikami, Doju

doi:10.1073/pnas.84.12.4327

Cited by 639 publications

(361 citation statements)

References 40 publications

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“…We found that the HVA Ca 2+ current of chick DRG neurons inactivates in a biphasic manner, and that the rapid phase of inactivation is diminished relative to the slow phase when the holding potential from which currents are elicited is depolarized, as others have reported previously (Nowycky et al, 1985;Fox et al, 1987a;Swandulla and Armstrong, 1988). These kinetics cannot be ascribed to the presence of N-and L-type channels as originally suggested (Nowycky et al, 1985) because our studies were confined to t0-CgTx-sensitive, N-type current (Kasai, Aosaki, and Fukuda, 1987;McCleskey, Fox, Feldman, Cruz, Olivera, Tsien, and Yoshikami, 1987;Plummer et al, 1989;Swandulla et al, 1991). Similar inactivation properties have been observed for the N current of rat sympathetic (Plummer et al, 1989), rat DRG (Regan et al, 1991), and frog sympathetic neurons (Jones and Marks, 1989).…”

Section: Discussionmentioning

confidence: 46%

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Cox

Dunlap

1994

The Journal of General Physiology

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We have studied the inactivation of high-voltage-activated (HVA), t0-conotoxin-sensitive, N-type Ca 2+ current in embryonic chick dorsal root ganglion (DRG) neurons. Voltage steps from -80 to 0 mV produced inward Ca ~+ currents that inactivated in a biphasic manner and were fit well with the sum of two exponentials (with time constants of ~ 100 ms and > 1 s). As reported previously, upon depolarization of the holding potential to -40 mV, N current amplitude was significantly reduced and the rapid phase of inactivation all but eliminated (Nowycky, M. C., A. P. Fox, and R. W. be explained by a model in which N channels inactivate by both fast and slow voltage-dependent processes. Alternatively, kinetic models of Ca-dependent inactivation suggest that the biphasic kinetics and holding-potential-dependence of N current inactivation could be due to a combination of Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish between these possibilities we have performed several experiments to test for the presence of Cadependent inactivation. Three lines of evidence suggest that N channels inactivate in a Ca-dependent manner. (a) The total extent of inactivation increased 50%, and the ratio of rapid to slow inactivation increased ~ twofold when the concentration of the Ca 2 § buffer, EGTA, in the patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally increased when the extracellular Ca 2 § concentration was raised from 0.5 to 5 mM. (c) Substituting Na § for Ca 2 § as the permeant ion eliminated the rapid phase of inactivation. Other results do not support the notion of current-dependent inactivation, however. Although high intraceUular EGTA (10

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Section: Discussionmentioning

confidence: 46%

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Cox

Dunlap

1994

The Journal of General Physiology

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“…On the basis of electrophysiological evidence it has been suggested that this toxin blocks both L and N type neuronal VSCC (McCleskey et al, 1987;Cruz et al, 1987), consistent with the suggestion that release is mediated principally by these two channel types (Miller, 1987). However neurotransmitter release has not always been found to be sensitive to co-conotoxin, perhaps reflecting heterogeneity of VSCC between different types of neurone (Anderson & Harvey, 1987;Sano et al, 1987;Maggi et al, 1988).…”

Section: Introductionmentioning

confidence: 74%

Evidence for a dihydropyridine‐sensitive and conotoxin‐insensitive release of noradrenaline and uptake of calcium in adrenal chromaffin cells

Owen¹,

Marriott²,

Boarder³

1989

British J Pharmacology

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“…Thus, application of nifedipine (10 PM), a blocker of L-type Ca 2+ channels, had little effect on the Ca2+ current elicited by a step to 0 mV from a holding potential of -60 mV (mean decrease of 12.5 f 10.5%, mean + SEM; n = 4). In contrast, application of w-conotoxin (16 FM), a blocker of N-type Ca*+ channels (McCleskey et al, 1987;Plummer et al, 1989), inhibited the total Ca*+ current by 70 + 7.6% (n = 5; data not shown). …”

Section: Ss and Ne Inhibit High-threshold Calcium Currentsmentioning

confidence: 94%

Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons

Golard

Siegelbaum

1993

J. Neurosci.

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Neurotransmitter inhibition of calcium currents (ICa) can be relieved by large depolarizing prepulses. This effect has been postulated to be due either to the voltage-dependent unbinding of an inhibitory molecule from the channel or to a slow voltage-dependent gating step intrinsic to the modulated channel. According to the first hypothesis, the rate of reinhibition (reblock) following a depolarizing prepulse should depend on the concentration of active inhibitory molecules and thus should increase with the extent of inhibition. To distinguish between these models we examined the actions of norepinephrine (NE) and somatostatin (SS) on high-threshold calcium currents in chick sympathetic ganglia, using whole-cell voltage-clamp methods. As previously described in other systems, both NE and SS inhibit omega- conotoxin-sensitive N-type Ca2+ current in a voltage-dependent manner. Pertussis toxin (PTX) pretreatment prevents the inhibition of the current, while replacing GTP in the patch pipette with GTP-gamma-S results in irreversible inhibition, consistent with the involvement of a PTX-sensitive G-protein. The inhibitory responses to NE and SS are not additive, suggesting that they act at a common locus. The inhibitory response to repeated applications of NE or SS desensitizes, with little evidence for cross desensitization. The inhibition of ICa is relieved by a 15 msec prepulse to +100 mV. Following repolarization to -80 mV, ICa slowly reblocks. During prolonged applications of NE or SS the extent of inhibition decreases due to desensitization and reblock kinetics are significantly slowed (time constant increases from 60 msec to > 100 msec for both NE and SS). These results are well fit by a quantitative model in which the kinetics of reblock reflect the binding of an inhibitory molecule to the channel.

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Omega-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle.

Cited by 639 publications

References 40 publications

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Evidence for a dihydropyridine‐sensitive and conotoxin‐insensitive release of noradrenaline and uptake of calcium in adrenal chromaffin cells

Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons

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