VIP inhibits N-type Ca2+ channels of sympathetic neurons via a pertussis toxin-insensitive but cholera toxin-sensitive pathway

Zhu, Yanbing; Ikeda, Stephen R.

doi:10.1016/0896-6273(94)90033-7

Cited by 95 publications

(78 citation statements)

References 50 publications

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“…Thus, although it remains possible that ␣ 1E channels are normally regulated through an exceedingly restricted direct G-protein pathway that we have missed, this seems unlikely. It should be noted in this regard that although N channel inhibition tends to be mediated by PTX-sensitive G-proteins, there are several examples of non-PTX-sensitive G-proteins also producing this type of direct, membrane-delimited inhibition (Hille, 1994;Zhu and Ikeda, 1994). This implies that for N channels, many types of G-protein ␣ subunits may be able to interact with the channel.…”

Section: Discussionmentioning

confidence: 99%

Selective G-Protein Regulation of Neuronal Calcium Channels

Tóth¹,

Shekter²,

Hui³

et al. 1996

J. Neurosci.

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We examined the properties and regulation of Ca channels resulting from the expression of human ␣ 1B and ␣ 1E subunits stably expressed in HEK293 cells. The ancillary subunits ␤ 1B and ␣ 2 /␦ were also stably expressed in these cell lines. Ca currents in ␣ 1B -expressing cells had the properties of N-type currents. Ca currents in cells expressing ␣ 1E exhibited a novel profile that was similar to the properties of the "R type" Ca current. Introduction of GTP-␥-S into ␣ 1B cells greatly enhanced the extent of prepulse facilitation of the Ca current, whereas it had only a very small effect in ␣ 1E -expressing cells. Activation of somatostatin receptors endogenous to HEK293 cells or opioid receptors, expressed in the cells after transfection, inhibited Ca currents in ␣ 1B -expressing cells. This inhibition was blocked by pertussis toxin and was partially relieved by a depolarizing prepulse. In contrast, no inhibitory effects were noted in cells expressing ␣ 1E channels under the same circumstances. HEK293 cells normally contained G-proteins from all of the four major families. Inhibition of Ca currents by agonists in ␣ 1B -expressing cells was enhanced slightly by the cotransfection of several G-protein ␣ subunits. agonists, however, had no effect in ␣ 1E -containing cells, even after overexpression of different G-protein ␣-subunits. In summary, these results demonstrate that there is a large difference in the susceptibility of ␣ 1B -and ␣ 1E -based Ca channels to regulation by G-proteins. This is so despite the fact that the two types of Ca channels show substantial similarities in their primary sequences.

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Section: Discussionmentioning

confidence: 99%

Selective G-Protein Regulation of Neuronal Calcium Channels

Tóth¹,

Shekter²,

Hui³

et al. 1996

J. Neurosci.

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“…The neuromodulators described above act either solely through a membrane-delimited pathway using a PTX-sensitive G o protein or one additional pathway (7). We also tested a neuromodulator that activates a pathway that does not use G o (36). After a 15-s incubation with 1 M secretin, which acts through G s , the NE secretion was 56% of the control value ( Fig.…”

Section: Neurobiology: Koh and Hillementioning

confidence: 99%

Modulation by neurotransmitters of catecholamine secretion from sympathetic ganglion neurons detected by amperometry

Koh

Hille

1997

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

106

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Many neuromodulators inhibit N-type Ca 2؉ currents via G protein-coupled pathways in acutely isolated superior cervical ganglion (SCG) neurons. Less is known about which neuromodulators affect release of norepinephrine (NE) at varicosities and terminals of these neurons. To address this question, we used carbon fiber amperometry to measure catecholamine secretion evoked by electrical stimulation at presumed sites of high terminal density in cultures of SCG neurons. The pharmacological properties of action potential-evoked NE release paralleled those of N-type Ca 2؉ channels: Release was completely blocked by Cd 2؉ or -conotoxin GVIA, reduced 50% by 10 M NE or 62% by 2 M UK-14,304, an ␣ 2 -adrenergic agonist, and reduced 63% by 10 M oxotremorine M (Oxo-M), a muscarinic agonist. Consistent with action at M 2 or M 4 receptor subtypes, Oxo-M could be antagonized by 10 M muscarinic antagonists methoctramine and tropicamide but not by pirenzepine. After overnight incubation with pertussis toxin, inhibition by UK-14,304 and Oxo-M was much reduced. Other neuromodulators known to inhibit Ca 2؉ channels in these cells, including adenosine, prostaglandin E 2 , somatostatin, and secretin, also depressed secretion by 34-44%. In cultures treated with -conotoxin GVIA, secretion dependent on L-type Ca 2؉ channels was evoked with long exposure to high K ؉ Ringer's solution. This secretion was not sensitive to UK-14,304 or Oxo-M. Evidently, many neuromodulators act on the secretory terminals of SCG neurons, and the depression of NE release at terminals closely parallels the membrane-delimited inhibition of N-type Ca 2؉ currents in the soma.Patch-clamp technique studies have shown that N-type Ca 2ϩ channels of the cell soma are modulated via many different G protein-coupled neurotransmitter receptors in superior cervical ganglion (SCG) neurons (1-6; for review, see ref. 7). Many neurotransmitter receptors, including ␣ 2 -adrenergic, somatostatin, prostaglandin E 2 (PGE 2 ), adenosine, M 4 muscarinic, pancreatic polypeptide, secretin, vasoactive intestinal peptide, and substance P, inhibit by a fast, membrane-delimited mechanism (7). Angiotensin II receptors and M 1 muscarinic receptors inhibit Ca 2ϩ channels via a slow, diffusible cytoplasmic messenger.Despite intensive work dissecting different modulatory pathways and investigating their underlying mechanisms (7-9), definite physiological roles for Ca 2ϩ channel inhibition in SCG cells have not yet been determined. Two have been proposed (7, 10): (i) In the soma, inhibition of Ca 2ϩ entry could alter cell excitability and action potential firing patterns because the somata possess Ca 2ϩ -activated K ϩ channels and Ca 2ϩ -sensitive M-type K ϩ channels (11-13), and (ii) at sympathetic nerve terminals and varicosities, inhibition of Ca 2ϩ influx could decrease norepinephrine (NE) secretion, as in Dunlap and Fischbach's (14) general concept of presynaptic inhibition. This hypothesis would require that N-type Ca 2ϩ channels be functionally coupled to many receptors at the dist...

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“…However, activation of some receptors linked to G s -proteins such as vasoactive intestinal polypeptide (VIP) receptor can also result in VD I Ca inhibition (Zhu and Ikeda, 1994). To differentiate these possibilities, we tested the effect of overnight pretreatment with PTX (0.5 g/ml; 16 -24 hr) on hSNSR4-mediated I Ca inhibition.…”

Section: Heterologously Expressed Hsnsr4 Couples To Voltagedependent Camentioning

confidence: 99%

Modulation of Ion Channels and Synaptic Transmission by a Human Sensory Neuron-Specific G-Protein-Coupled Receptor, SNSR4/mrgX1, Heterologously Expressed in Cultured Rat Neurons

Chen¹,

Ikeda²

2004

J. Neurosci.

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Human sensory neuron-specific G-protein-coupled receptors (SNSRs) are expressed solely in small diameter primary sensory neurons. This restricted expression pattern is of considerable therapeutic interest because small nociceptors transmit chronic pain messages. The neuronal function of human SNSRs is difficult to assess because rodent orthologs have yet to be clearly defined, and individual isoforms are found only in a small subset of primary sensory neurons. To circumvent this problem, we expressed human SNSR4 (hSNSR4; also known as Hs.mrgX1) in rat superior cervical ganglion (SCG), dorsal root ganglion (DRG), and hippocampal neurons using nuclear injection or recombinant adenoviruses and examined modulation of ion channels and neurotransmission using whole-cell patch-clamp techniques. BAM8 -22 (a 15 amino acid C-terminal fragment of bovine adrenal medulla peptide 22), a peptide agonist derived from proenkephalin, inhibited high (but not low) voltage-activated Ca 2ϩ current in both DRG and SCG neurons expressing hSNSR4, whereas no response was detected in control neurons. The Ca 2ϩ current inhibition was concentration dependent and partially sensitive to Pertussis toxin (PTX) treatment. Additionally, the peptide was highly effective in modulating current arising from M-type K ϩ channels in SCG neurons expressing hSNSR4. In hippocampal neurons expressing hSNSR4, BAM8 -22 induced presynaptic inhibition of transmission that was abolished after PTX treatment. Our data indicate that hSNSR4, when heterologously expressed in rat neurons, can be activated by an opioid-related peptide, couples to G q/11 -proteins as well as PTX-sensitive G i/o -proteins, and modulates neuronal Ca 2ϩ channels, K ϩ channels, and synaptic transmission.

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VIP inhibits N-type Ca2+ channels of sympathetic neurons via a pertussis toxin-insensitive but cholera toxin-sensitive pathway

Cited by 95 publications

References 50 publications

Selective G-Protein Regulation of Neuronal Calcium Channels

Selective G-Protein Regulation of Neuronal Calcium Channels

Modulation by neurotransmitters of catecholamine secretion from sympathetic ganglion neurons detected by amperometry

Modulation of Ion Channels and Synaptic Transmission by a Human Sensory Neuron-Specific G-Protein-Coupled Receptor, SNSR4/mrgX1, Heterologously Expressed in Cultured Rat Neurons

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