Neurotransmitter modulation of calcium channels in rat sympathetic neurons

Plummer, Andrew; Rittenhouse, Ann R.; Kanevsky, Max; Hess, Peter

doi:10.1523/jneurosci.11-08-02339.1991

Cited by 86 publications

(43 citation statements)

References 65 publications

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“…Also in agreement with previous results, we find that Ca2+ channel inhibition depends on the activation of a PTX-sensitive G-protein and does not appear to be mediated by AA or PKC activation (Kasai and Aosaki, 1989;Bley and Tsien, 1990;Plummer et al, 1991).…”

Section: Discussionsupporting

confidence: 93%

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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Section: Discussionsupporting

confidence: 93%

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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“…Results from other studies on the sensitivity to pertussis toxin of the noradrenaline modulatory pathway have provided conflicting conclusions. Noradrenaline inhibition of calcium currents in sympathetic neurones has been found to be pertussis-toxin sensitive by some (rat superior cervical ganglion: Plummer et al, 1991; rat superior cervical ganglion: Schofield, 1991; chick paravertebral ganglion: Boehm et al, 1992) and insensitive or partially sensitive by others (rat superior cervical ganglion: Song et al, 1989;. Similarly the effects of noradrenaline on neurotransmitter release via a2-adrenoceptors have been described as pertussis toxin-sensitive (Allgaier et al, 1985;Boehm et al, 1992) and insensitive (Musgrave et al, 1987;Docherty, 1990;Murphy & Majewski, 1990).…”

Section: Effects Ofpertussis Toxin On Inhibition Of K+-evoked Overflomentioning

confidence: 99%

Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture

Hill

Powis

Hendry

1993

British J Pharmacology

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1 Sympathetic neurones derived from superior cervical ganglia of neonatal rats and maintained in tissue culture were used to investigate the modulation of neurotransmitter release by presynaptic receptors. Three week old cultures of neurones were loaded with [3H]-noradrenaline to label endogenous neurotransmitter stores. Release of noradrenaline was evoked by depolarization with raised extracellular K+ in the presence of desipramine and corticosterone to prevent uptake of released catecholamine. 2 Potassium (55 mmol 1-) depolarization for 30 s caused more than a four fold increase in 3H overflow from basal levels but this increase was reduced by up to 40% in the presence of exogenous noradrenaline (1 timol 1`). The inhibition by noradrenaline of depolarization-evoked overflow was blocked by the aI/a2-adrenoceptor antagonist, phentolamine. Phentolamine alone did not increase K+-evoked 3H overflow. 3 The a2-adrenoceptor antagonist, yohimbine, produced a concentration-dependent block of the inhibition by noradrenaline of K+-evoked overflow, while the ax-adrenoceptor antagonist, prazosin, was without effect at concentrations up to 0.1 Lmol 1'. 4 The P-adrenoceptor antagonist, propranolol, neither reduced K+-evoked overflow nor increased the degree of inhibition caused by the addition of 1 1tmol 1' noradrenaline.5 The M2-adrenoceptor agonist, clonidine (I iLmol 11) was less effective than noradrenaline at inhibiting K+-evoked overflow, while the a,-adrenoceptor agonist, phenylephrine (1,umol 1I) had no significant effect.6 The L-channel calcium blocker, nicardipine (1 timol 1-') significantly inhibited 3H overflow evoked by K+. In the presence of L-channel block, however, noradrenaline still inhibited residual evoked overflow. 7 In the presence or absence of nicardipine, pertussis toxin pretreatment (1 nmol 1-') reduced, but did not prevent, the effect of noradrenaline (1 tLmol 1'). Pertussis toxin alone caused a significant enhancement of K+-evoked 3H overflow. 8 The data indicate that on postganglionic neurones of cultured rat sympathetic ganglia there are M2-adrenoceptors that modulate neurotransmitter release, but no functional P-adrenoceptors that mediate an enhancement of transmitter release. The data suggest further that in this preparation the mechanism of a2-adrenoceptor modulation may involve pertussis toxin sensitive and insensitive G-proteins and effects on calcium channels other than L-type.

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“…This interpretation requires some caution, however, as there are numerous discrepancies in the literature regarding the PTX sensitivity of neurotransmitter inhibition of rat sympathetic neurone Ca2+ currents. For example, Plummer et al (1991) and Schofield (1991) report that the response to NA is abolished (or nearly so) by PTX pretreatment while Bernheim, Beech & Hille (1990) and Song, Saito, Noguchi & Konishi (1991) report that a significant portion of the NA response remains after PTX pretreatment. Similarly, Wanke et al (1987), Plummer et al (1991), and Song et al (1991) report that Ca2+ current inhibition induced by muscarinic agonists is eliminated by PTX pretreatment while Bernheim et al (1990) report a 'PTX-resistant' component to muscarinic agonist-induced block.…”

Section: S R Ikeda Effect Of Pge2 On ( +)202-791-induced Tail Currentsmentioning

confidence: 99%

“…For example, Plummer et al (1991) and Schofield (1991) report that the response to NA is abolished (or nearly so) by PTX pretreatment while Bernheim, Beech & Hille (1990) and Song, Saito, Noguchi & Konishi (1991) report that a significant portion of the NA response remains after PTX pretreatment. Similarly, Wanke et al (1987), Plummer et al (1991), and Song et al (1991) report that Ca2+ current inhibition induced by muscarinic agonists is eliminated by PTX pretreatment while Bernheim et al (1990) report a 'PTX-resistant' component to muscarinic agonist-induced block. Thus, experimental conditions, especially pipette solutions (Beech et al 1991), probably have a significant influence on the outcome of such experiments.…”

Section: S R Ikeda Effect Of Pge2 On ( +)202-791-induced Tail Currentsmentioning

confidence: 99%

“…It is acknowledged that several alternative models regarding G protein-mediated inhibition of Ca2+ channels have been proposed (Grassi & Lux, 1989;Kasai & Aosaki, 1989;Marchetti & Robello, 1990;Lopez & Brown, 1991;Kasai, 1992), further studies are required to discriminate among these possibilities. Two experiments, based on those used by Plummer et al (1991), were undertaken to determine whether PGE2 had a selective effect on a particular Ca2+ current component. First, the ability of PGE2 to modulate L-type channels was assessed on the prolonged tail current induced by (+)202-791.…”

Section: Mechanism Of Prostaglandin Blockmentioning

confidence: 99%

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Prostaglandin modulation of Ca2+ channels in rat sympathetic neurones is mediated by guanine nucleotide binding proteins.

Ikeda

1992

The Journal of Physiology

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SUMMARY1. The effects of prostaglandins on whole-cell Ca21 currents of acutely isolated and short-term cultured adult rat superior cervical ganglion neurones were investigated using the patch-clamp technique.2. Prostaglandin E2 (PGE2) produced a rapid, reversible and concentrationdependent reduction of the sympathetic neurone Ca2+ current. The effects of PGE2 were both voltage and time dependent. The relationship between Ca2+ current inhibition and test potential was 'bell' shaped with maximal inhibition occurring near the potential where the Ca2+ current amplitude was maximal (ca+ 10 mV). In the presence of PGE2, the Ca2+ current rising phase was slower and biphasic at potentials between 0 and + 40 mV.3. Prolonged (> 2 min) application of 1 ,M PGE2 resulted in a desensitization of the response. Similarly, repeated short (ca 1 min) applications of 1 /SM PGE2 resulted in a progressive tachyphylaxis of the response. 4. A concentration-response curve for PGE2 was well described by a single-site binding isotherm. The concentration producing half-maximal block (IC50) and the maximal attainable reduction of the Ca2+ current were 7-8 nm and 48 %, respectively.5. When compared at a concentration of 1 /M, PGF2a was less potent (33% inhibition) than PGE2 but otherwise produced similar effects. In contrast, 1 /SM PGD2 had negligible effects.6. Activation curves, as derived from tail current amplitudes, were described by the sum of two Boltzmann functions in both the presence and absence of PGE2. In the presence of PGE2, the activation curve was shifted toward more depolarized potentials. Most of the shift could be accounted for by a decrease in the fractional amplitude of the current component activated at hyperpolarized potentials along with a concomitant increase in the component activated at depolarized potentials. The deactivation time constant (0 33 ms), measured at -40 mV, was not altered by PGE2. 7. The majority of the Ca2+ current inhibition produced by PGE2 was relieved by depolarizing conditioning pre-pulses to + 80 mV for 50 ms. Ca2+ current. Pretreatment of the neurones overnight with pertussis toxin significantly, but incompletely, decreased the Ca2+ current inhibition produced by PGE2. 9. The prolonged Ca2+ tail current component induced by the dihydropyridine Ca2`channel 'agonist' (+ )202-791 (2 JM) was unaffected by 1 UM PGE2.10. PGE2 partially inhibited the Ca2+ current component remaining after pretreatment of the neurones with 10 tim w-conotoxin.11. It is concluded that PGE2 produces a voltage-dependent depolarizing shift in the activation of N-type Ca2+ channels resulting in an attenuation of the whole-cell Ca2+ current over a limited voltage range. The shift can be accommodated by a hypothesis in which Ca2+ channels shift from a 'willing' to a 'reluctant' state.Results from experiments with guanine nucleotide analogues and pertussis toxin provide evidence that guanine nucleotide regulatory proteins are involved in the transduction of this response.

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Neurotransmitter modulation of calcium channels in rat sympathetic neurons

Cited by 86 publications

References 65 publications

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

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

Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture

Prostaglandin modulation of Ca2+ channels in rat sympathetic neurones is mediated by guanine nucleotide binding proteins.

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