Effects of N‐, P‐ and Q‐type neuronal calcium channel antagonists on mammalian peripheral neurotransmission

Wright, Christine E.; Angus, James A.

doi:10.1111/j.1476-5381.1996.tb15676.x

Cited by 78 publications

(55 citation statements)

References 43 publications

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“…The average s.e.mean within tissues (or rabbits) was calculated from repeated measures analysis of variance (ANOVA) using the pooled estimate of error from the residual mean square as (error mean square/number of tissues, or rabbits) 0.5 after sums of squares between tissues (or rabbits) and between peptide concentrations (or times) had been subtracted from the total sums of squares for each treatment group (Snedecor & Cochran, 1989). These average s.e.means are located on the lines shown in Figures 1, 4 and 5 (Wright et al, 1987;Wright & Angus, 1996). For rat atrium, mesenteric artery and vas deferens experiments, sympathetic responses were compared within and between groups by repeated measures ANOVA with Greenhouse-Geisser correction for correlation (Ludbrook, 1994), calculated by means of the statistical program SuperANOVA TM 1.11 for Macintosh.…”

Section: Analyses and Statistical Methodsmentioning

confidence: 99%

“…CVID was 10 fold less potent in the mesenteric artery preparation compared with the vas deferens or atrium assay. Importantly, the sympathetic nerves were stimulated with parameters that were N-type voltage-operated calcium channel blocker-sensitive (100%) to avoid confounding the assay estimate of pIC 50 with N-channel-resistant (perhaps P/Q channel-sensitive) responses (see Wright & Angus, 1996;Sanger et al, 2000). These isolated tissue assays allowed a direct comparison of oset rates of CVID and MVIIA in three tissues.…”

Section: In Vitro Assaysmentioning

confidence: 99%

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Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Wright

Robertson

Whorlow

et al. 2000

British J Pharmacology

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1 The eects of a novel N-type voltage-operated calcium channel antagonist, o-conotoxin CVID, were compared with o-conotoxin MVIIA on sympathetic-evoked activation of right atria (RA), small mesenteric arteries (MA) and vasa deferentia (VD) isolated from the rat. Their eects were also compared on blood pressure and cardiovascular re¯exes in conscious rabbits. 2 The pIC 50 values for MVIIA and CVID, respectively, for inhibiting sympathetic-evoked responses were equivalent in RA (8.7 and 8.7) and VD (9.0 and 8.7); however, in MA the values were 8.4 and 7.7. The cardiac to vascular (RA/MA) potency ratios, antilog (plog RA ± plog MA), for MVIIA and CVID were 2 and 10. The oset rates for CVID and MVIIA were rapid, and peptide reapplication caused rapid onset of blockade, suggesting limited desensitization. 3 In the conscious rabbit, CVID and MVIIA (100 mg kg 71 i.v.) caused a similar fall in blood pressure and a tachycardia that rapidly reached maximum. Both peptides decreased the vagal-and sympathetic-mediated components of the barore¯ex, but had no eect on the vagal nasopharyngeal re¯ex. The orthostatic re¯ex to 908 tilt was blocked by MVIIA with sustained postural hypotension for 590 min after administration. In contrast, CVID caused postural hypotension at 30 min which recovered rapidly. 4 Neither CVID nor MVIIA (3 mg kg 71 i.t.) signi®cantly altered cardiovascular variables or autonomic re¯exes. 5 In conclusion, CVID appears to be relatively weak at inhibiting the re¯ex response to tilt consistent with its weaker inhibition of rat mesenteric artery constriction to perivascular nerve stimulation. This may point to subtype N-type calcium channel selectivity.

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Section: Analyses and Statistical Methodsmentioning

confidence: 99%

Section: In Vitro Assaysmentioning

confidence: 99%

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Wright

Robertson

Whorlow

et al. 2000

British J Pharmacology

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“…Moreover, different voltage-gated calcium channels can be coupled to transmitter release during low-versus highfrequency electrical stimulation (Wright and Angus, 1996). Therefore, we next sought to determine the requirement for specific voltage-activated calcium channels in BDNF release evoked by different patterns of stimulation.…”

Section: Release Of Native Bdnf Evoked By Patterned Electrical Stimulmentioning

confidence: 99%

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

2002

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Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent modifications of neuronal connectivity and synaptic strength, including establishment of hippocampal long-term potentiation (LTP). To shed light on mechanisms underlying BDNF-dependent synaptic plasticity, the present study was undertaken to characterize release of native BDNF from newborn rat hippocampal neurons in response to physiologically relevant patterns of electrical field stimulation in culture, including tonic stimulation at 5 Hz, bursting stimulation at 25 and 100 Hz, and theta-burst stimulation (TBS). Release was measured using the ELISA in situ technique, developed in our laboratory to quantify secretion of native BDNF without the need to first overexpress the protein to nonphysiological levels. Each stimulation protocol resulted in a significant increase in BDNF release that was tetrodotoxin sensitive and occurred in the absence of glutamate receptor activation. However, 100 Hz tetanus and TBS, stimulus patterns that are most effective in inducing hippocampal LTP, were significantly more effective in releasing native BDNF than lower-frequency stimulation. For all stimulation protocols tested, removal of extracellular calcium, or blockade of N-type calcium channels, prevented BDNF release. Similarly, depletion of intracellular calcium stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffeine-ryanodine-sensitive stores, markedly inhibited activity-dependent BDNF release. Our results indicate that BDNF release can encode temporal features of hippocampal neuronal activity. The dual requirement for calcium influx through N-type calcium channels and calcium mobilization from intracellular stores strongly implicates a role for calcium-induced calcium release in activity-dependent BDNF secretion.

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“…Of the multiple subtypes of voltage-gated calcium channel current (I Ca ), it has been shown that calcium influx via the N-, P, and Q-subtypes triggers neurotransmission at central and peripheral synapses (Luebke et al, 1993;Takahashi and Momiyama, 1993;Regehr and Mintz, 1994;Wheeler et al, 1994;Waterman, 1996;Wright and Angus, 1996). N-type channels are identified pharmacologically as being blocked irreversibly by -conotoxin GVIA (-Cgtx GVIA) (McCleskey et al, 1987;Plummer et al, 1989) and are encoded for by the class B ␣ 1 subunit gene (Dubel et al, 1992;Williams et al, 1992).…”

Section: Abstract: Calcium Channel; G-protein; Atp; Inhibition; Patcmentioning

confidence: 99%

Comparison of N- and P/Q-Type Voltage-Gated Calcium Channel Current Inhibition

1997

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Activation of N-and P/Q-type voltage-gated calcium channels triggers neurotransmitter release at central and peripheral synapses. These channels are targets for regulatory mechanisms, including inhibition by G-protein-linked receptors. Inhibition of P/Q-type channels has been less well studied than the extensively characterized inhibition of N-type channels, but it is thought that they are inhibited by similar mechanisms although possibly to a lesser extent than N-type channels. The aim of this study was to compare the inhibition of the two channel types.Calcium currents were recorded from adrenal chromaffin cells and isolated by the selective blockers -conotoxin GVIA (1 M) and -agatoxin IVA (400 nM). The inhibition was elicited by ATP (100 M) or intracellular application of GTP-␥-S. It was classified as voltage-sensitive (relieved by a conditioning prepulse) or voltage-insensitive (present after a conditioning prepulse). The voltage-insensitive inhibition accounted for a 20% reduction of both currents, whereas the voltage-sensitive inhibition reduced the N-type current by 45% but the P/Q-type current by 18%. However, the voltage dependence of the inhibition, the time course of relief from inhibition during a conditioning prepulse, and the time course of reinhibition after such a prepulse showed few differences between the N-and P/Q-type channels. Assuming a simple bimolecular reaction, our data suggest that changes in the kinetics of the G-protein/ channel interaction alone cannot explain the differences in the inhibition of the N-and P/Q-type calcium channels. The subtle differences in inhibition may facilitate the selective regulation of neurotransmitter release. Key words: calcium channel; G-protein; ATP; inhibition; patch clamp; GTP-␥-S; N-type calcium channel; P/Q-type calcium channelOf the multiple subtypes of voltage-gated calcium channel current (I Ca ), it has been shown that calcium influx via the N-, P, and Q-subtypes triggers neurotransmission at central and peripheral synapses (Luebke et al

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Effects of N‐, P‐ and Q‐type neuronal calcium channel antagonists on mammalian peripheral neurotransmission

Cited by 78 publications

References 43 publications

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

Comparison of N- and P/Q-Type Voltage-Gated Calcium Channel Current Inhibition

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