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S R Ikeda

Publications and source records attributed to S R Ikeda.

At least 37 records · Page 2Linked to original sources
PubMed1998

SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversal of tonic CB1 cannabinoid receptor activity.

The CB1 cannabinoid receptor antagonist SR 141716A abolished the inhibition of Ca2+ currents by the agonist WIN 55,212-2. However, SR 141716A alone increased Ca2+ currents, with an EC50 of 32 nM, in neurons that had been microinjected with CB1 cRNA. For an antagonist to elicit an effect, some receptors must be tonically active. Evidence for tonically active CB1 receptors was seen as enhanced tonic inhibition of Ca2+ currents. Preincubation with anandamide failed to enhance the effect of SR 141716A, indicating that anandamide did not cause receptor activity. Under Ca2+-free conditions designed to block the Ca2+-dependent formation of anandamide and sn-2-arachidonylglycerol, SR 141716A again increased the Ca2+ current. The Ca2+ current was tonically inhibited in neurons expressing the mutant K192A receptor, which has no affinity for anandamide, demonstrating that this receptor is also tonically active. SR 141716A had no effect on the Ca2+ current in these neurons, but SR 141716A could still antagonize the effect of WIN 55, 212-2. Thus, the K192 site is critical for the inverse agonist activity of SR 141716A. SR 141716A appeared to become a neutral antagonist at the K192A mutant receptor. Native cannabinoid receptors were studied in male rat major pelvic ganglion neurons, where it was found that WIN 55,212-2 inhibited and SR 141716A increased Ca2+ currents. Taken together, our results demonstrate that a population of native and cloned CB1 cannabinoid receptors can exist in a tonically active state that can be reversed by SR 141716A, which acts as an inverse agonist.

Animals↗
PubMed1997

Molecular cloning of a putative tetrodotoxin-resistant sodium channel from dog nodose ganglion neurons.

Voltage-gated tetrodotoxin (TTX)-resistant sodium channels present in primary sensory neurons may be responsible for the excitability of nociceptors, and may underlie pain and tenderness associated with tissue injury and inflammation. Here, we report the cloning of a putative sodium channel (NaNG) from dog nodose ganglia. The sequence of the full-length cDNA predicts an open reading frame of 5886 nucleotides encoding a protein of 1962 amino acids. The predicted protein shows 82.3% identity with the recently discovered TTX-resistant sodium channel (SNS/PN3). In the TTX-binding site, a serine appears as in TTX-resistant SNS/PN3, instead of Cys (as in TTX-insensitive cardiac channels) and Tyr/Phe (as in TTX-sensitive sodium channels). Coupled transcription and translation of full-length cDNA produced a 220-kDa protein; based on Northern blot and RT-PCR analysis, its expression is restricted to nodose ganglia, and not present in cortex, hippocampus, cerebellum, liver, heart or skeletal muscle. We propose that NaNG might be a new member of the TTX-resistant sodium channel family expressed in sensory neurons.

Amino Acid Sequence↗
PubMed1997

Heterologous expression of a P2x-purinoceptor in rat chromaffin cells detects vesicular ATP release.

A cloned P2x-purinoceptor was transiently expressed in single isolated rat adrenal chromaffin cells and evaluated for the detection of released ATP. After cytoplasmic injection of the P2x complementary RNA (cRNA; 4-24 h), application of ATP produced an inwardly rectifying current over the voltage range -130 to -10 mV as measured by the whole cell patch-clamp technique. The dose-response curve for ATP was sigmoidal with a 50% effective concentration of 18. 2 microM. Suramin, a P2x-antagonist, attenuated the ATP-induced current. Depolarizing voltage pulses to 0 mV or application of histamine, stimuli that trigger exocytosis, resulted in the appearance of suramin-sensitive spontaneous transient inward currents (at -60 mV) that resembled excitatory postsynaptic currents although they were slower in time course. Concurrent detection of catecholamine release with a carbon fiber electrode often showed coincidence of the amperometric current with the synaptic currentlike events suggesting that ATP and catecholamines were released from the same vessicle. These data demonstrate that expression of a P2x-purinoceptor in chromaffin cells produces a functional autoreceptor capable of detecting vesicular release of ATP. In combination with carbon fiber amperometry, simultaneous vesicular release of two neurotransmitters from a single chromaffin cell could be monitored. The P2x-purinoceptor, however, produced a regenerative effect on release apparently resulting from the high Ca2+ permeability of the receptor. Thus modification of the P2x-purinoceptor would be required before the system could be applied to examining processes involved in stimulus-release coupling.

Adenosine Triphosphate↗
PubMed1997

Inhibition of M-type K+ and N-type Ca2+ channels by the human gonadotropin-releasing-hormone receptor heterologously expressed in adult neurons.

Gonadotropin-releasing hormone (GnRH) controls all aspects of reproductive function. GnRH is secreted by hypothalamic neurons and exerts its effects on the endocrine system through pituitary gonadotropes, while its effects on sexual receptivity are mediated by the central nervous system. The electrophysiological responses of central neurons to GnRH have shown both excitatory and inhibitory responses, but little is known about the mechanisms by which GnRH can change neuronal excitability. The present study addresses the mechanisms whereby stimulation of the human GnRH receptor changes neuronal excitability by using a combination of electrophysiological and heterologous expression techniques. Microinjection of in vitro transcribed cRNA coding for the human GnRH receptor into enzymatically dissociated adult rat superior cervical ganglion neurons resulted in GnRH receptor expression. Activation of the GnRH receptor inhibited both M-type K+ and N-type Ca2+ channels. Inhibition of M-type K+ channels was insensitive to pertussis toxin pretreatment and blocked by intracellular GDPbetaS. Inhibition of Ca2+ channels was slow in onset, voltage independent and insensitive to pertussis toxin. Wash-out of GnRH resulted in an unusual transient reversal of tonic G-protein-mediated Ca2+ channel inhibition. Block of the N-type Ca2+ channel with omega-conotoxin GVIA decreased Ca2+ current inhibition from 43 to 15%, indicating that the N-type Ca2+ channel is an effector target. Ca2+ channel inhibition was completely abolished by including a Ca2+ chelator in the patch pipette. Cell-attached macropatch experiments indicated that Ca2+ channel inhibition is mediated by a diffusible second messenger. These results demonstrate that the human GnRH receptor can inhibit M-type K+ and N-type Ca2+ channels when heterologously expressed in adult rat neurons. Modulation of M-type K+ and N-type Ca2+ channels in central neurons which contain GnRH receptors is likely to contribute to the changes in neuronal excitability elicited by GnRH.

Animals↗
PubMed1996

Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits.

The most commonly used signal transduction pathway for receptor-mediated N-type Ca2+-channel modulation involves activation of a heterotrimeric G protein to produce voltage-dependent inhibition. Although it is widely assumed that Galpha mediates this effect, experiments to address this hypothesis directly are lacking. Here I show that transient overexpression of Gbetagamma in sympathetic neurons mimics and occludes the voltage-dependent Ca2+ channel modulation produced by noradrenaline (NA). Conversely, over-expression of Galpha produces minimal effects on basal Ca2+ channel behaviour but attenuates NA-mediated inhibition in a manner consistent with the buffering of Gbetagamma. These observations indicate that it is Gbetagamma, and Galpha, that mediates voltage-dependent inhibition of N-type Ca2+ channels. The identification of Gbetagamma as the mediator of this pathway has broad implications as G-protein-coupled receptors, many of which are implicated in disease or are targets of therapeutic agents, couple to N-type Ca2+ channels and may modulate synaptic transmission by this mechanism.

Animals↗
PubMed1996

Inward currents underlying action potentials in rat adrenal chromaffin cells.

1. Current- and voltage-clamp studies were conducted on isolated rat adrenal chromaffin cells to identify the voltage-dependent ion channels mediating inward currents. 2. Mean resting membrane potential of the isolated cells was -62 +/- 3 (SE) mV. Evoked action potentials were both Na+ and Ca2+ based, and whole cell voltage-clamp studies in normal saline revealed an inward-rectifier-type current. 3. Na+ channels were studied in isolation and showed a half-inactivation of -60 +/- 2 mV with a slope factor of -6 mV and a half-activation of -26.8 +/- 2 mV with a slope factor of 6.5 +/- 0.7 mV. 4. Isolated Ca2+ currents, elicited in 10 mM external Ca2+, revealed a T-type current in a subset of cells. Ca2+ currents were sensitive to both N- and L-type channel antagonists, and blockade of the current by the L-type channel antagonist nimodipine and the N-type channel antagonist omega-conotoxin GVIA revealed a third Ca2+-current component that was unaffected by the P-type channel antagonist omega-agatoxin IVA. 5. Ca2+ currents were facilitated 5-20% by a depolarizing prepulse, and facilitation was completely blocked by nimodipine. The effects of the dihydropyridine L-type channel agonist, (+)202-791 and depolarizing prepulses on the currents were additive. 6. The results of this study show that the properties of voltage-dependent ion channels in rat chromaffin cells differ from those reported in their counterparts in bovine chromaffin cells. Na+ channels differ in activation and inactivation properties and Ca2+ channels differ in activation, sensitivity to antagonists, and the magnitude of voltage-dependent facilitation.

Action Potentials↗
PubMed1996

Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system.

Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzymatically dissociated adult rat superior cervical ganglion neurons. The cannabimimetic aminoalkylindole WIN 55,212-2 inhibited whole-cell Ca2+ currents in neurons injected 16-25 hr previously with rat brain CB1 cannabinoid receptor cRNA. Inhibition of the Ca2+ current was voltage and concentration dependent, with a maximal inhibition of 73% and an IC50 value of 47 nM. The synthetic cannabinoid analogue CP55,940 also inhibited Ca2+ currents, with a maximal inhibition of 38% and an IC50 value of 7 nM. Ca2+ current inhibition was blocked by inclusion of guanosine-5'-O-(2-thiodiphosphate) in the intracellular patch pipette solution or by pretreatment with pertussis toxin. Pretreatment with the N-type Ca2+ channel antagonist omega-conotoxin GVIA reduced the inhibition by 100 nM WIN 55,212-2 from 44% to 6%, indicating that N-type Ca2+ channels are a target of cannabinoid action. On washout of WIN 55,212-2, the Ca2+ current amplitude "overrecovered" in 47% of the neurons tested. Anandamide, the endogenous cannabimimetic compound, had an inconsistent effect on the voltage-dependent Ca2+ currents in the majority of neurons microinjected with cannabinoid receptor cRNA. Ca2+ channels were a specific effector target of the cannabinoid receptor, as two different K+ currents, the M current and the A current, were not modulated by the cannabimimetic WIN 55,212-2.

Animals↗
PubMed1995

Phenotype-specific expression of T-type calcium channels in neurons of the major pelvic ganglion of the adult male rat.

1. Neurons from the major pelvic ganglia (MPG) of adult male rats were enzymatically dissociated and the neurochemical phenotype and Ca2+ current properties examined. 2. Neurons were divided into two subpopulations based on the presence or absence of low threshold T-type Ca2+ channels. The subpopulation of neurons expressing T-type Ca2+ channels was characterized by a mean diameter of 34 microns, a mean membrane capacitance (Cm) of 72 pF, tyrosine hydroxylase immunoreactivity (TH-IR), a lack of NADPH diaphorase (NADPHd) reactivity and a high degree of alpha 2-adrenoceptor-mediated Ca2+ current inhibition (60%). 3. The subpopulation of neurons without overt T-type Ca2+ channels had a mean diameter of 23 microns, a mean Cm of 30 pF, a lack of TH-IR and a moderate degree of alpha 2-adrenoceptor-mediated Ca2+ current inhibition (27%). About 50% of this subpopulation stained positively for NADPHd. 4. The contribution of high threshold N-type Ca2+ channels (60-70%), as determined from omega-conotoxin GVIA inhibition, and L-type Ca2+ channels (< 10%), as determined from nifedipine inhibition, to the whole-cell Ca2+ current was similar for both subpopulations of neurons. 5. These data indicate that the MPG contain at least two subpopulations of postganglionic neurons, i.e. adrenergic and non-adrenergic, with distinct electrophysiological and neurochemical properties. Furthermore, we propose that the presence or absence of T-type Ca2+ channels provides an electrophysiological means of identifying adrenergic and non-adrenergic phenotype, respectively, in neurons of the male rat MPG.

Animals↗
PubMed1995

Permeation selectivity by competition in a delayed rectifier potassium channel.

Permeation selectivity was studied in two human potassium channels, Kv2.1 and Kv1.5, expressed in a mouse cell line. With normal concentrations of potassium and sodium, both channels were highly selective for potassium. On removal of potassium, Kv2.1 displayed a large sodium conductance that was inhibited by low concentrations of potassium. The channel showed a competition mechanism of selectivity similar to that of calcium channels. In contrast, Kv1.5 displayed a negligible sodium conductance on removal of potassium. The observation that structurally similar potassium channels show different abilities to conduct sodium provides a basis for understanding the structural determinants of potassium channel selectivity.

Animals↗
PubMed1995

Influence of permeating ions on potassium channel block by external tetraethylammonium.

1. Block by external tetraethylammonium (TEA) was examined on currents carried by potassium (K+) and sodium (Na+) through the cloned delayed rectifier K+ channel Kv2.1. 2. In the presence of high intracellular K+ and high extracellular Na+, currents through the Kv2.1 channel were carried almost exclusively by K+. In the absence of both intracellular and extracellular K+, large currents were carried by Na+ through the Kv2.1 channel. 3. External application of 30 mM TEA blocked K+ currents through Kv2.1 by 87%. The same external concentration of TEA had no effect on Na+ currents through this channel. 4. As the K+ concentration was increased between 0 and 140 mM, the percentage of current blocked by TEA progressively increased from 0 to 87%. 5. These data indicate that block of K+ channels by external TEA depends on the permeating ion. Furthermore, these data indicate that in the presence of Na+ and absence of K+, TEA does not bind to the channel, and that addition of low concentrations of K+ facilitates TEA binding.

Animals↗
PubMed1995

Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: subtype-specific coupling to ion channels.

A novel heterologous expression system was used to examine the coupling of metabotropic glutamate receptors (mGluRs) to neuronal voltage-gated ion channels. Cytoplasmic injection of mGluR2 cRNA into adult rat sympathetic neurons resulted in the expression of receptors that negatively coupled to N-type Ca2+ channels through a pertussis toxin-sensitive pathway. Injection of mGluR1 alpha cRNA resulted in the expression of receptors that inhibited M-type K+ channels via a pertussis toxin-insensitive pathway. Coupling was restricted to specific transduction elements and effectors, since mGluR2 did not inhibit M channels and mGluR1 alpha had minimal effects on Ca2+ channels. These findings demonstrate that heterologously expressed, and thus unambiguously identified, mGluR subtypes modulate specific neuronal ion channels through discrete signal transduction pathways.

Animals↗
PubMed1995

Phorbol ester potentiation of canine pulmonary vasoreactivity to histamine.

The effect of phorbol myristate acetate (PMA) on canine pulmonary vasoreactivity to histamine was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured by using vascular occlusion techniques. Histamine (10(-5) M) significantly increased postcapillary resistance by venoconstriction and significantly attenuated total vascular compliance by decreasing large-vessel compliance and middle-compartment compliance. Pretreatment with the phorbol ester PMA (10(-7) M) significantly potentiated the vasoactive response to histamine and elicited an edemagenic effect in the isolated dog lung through modulation of the histaminergic vasoconstrictor effect on precapillary resistance, postcapillary resistance, and pulmonary vascular compliance. Pretreatment with the protein kinase C inhibitors staurosporine (10(-7) M) and calphostin C (10(-6) M) and the dihydropyridine Ca2+ channel blocker nifedipine (10(-5) M) significantly attenuated the effect of PMA on histaminergic-mediated vasoconstriction. The results of this study indicate that phorbol esters may exert their effect on canine pulmonary vasoreactivity predominantly through activation of protein kinase C and influx of Ca2+ through voltage-dependent Ca2+ channels.

Alkaloids↗
PubMed1994

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

The best characterized Ca2+ channel modulation in mammalian sympathetic neurons is an inhibition of N-type channels via a pertussis toxin (PTX)-sensitive heterotrimeric G protein. Here, we show that vasoactive intestinal polypeptide (VIP), an abundant neuropeptide in the PNS and CNS, inhibited N-type Ca2+ channels in rat sympathetic neurons in a voltage-dependent, membrane-delimited manner. The effect of VIP was insensitive to PTX but was attenuated by cholera toxin or anti-Gs alpha antibodies. VIP-mediated inhibition was independent of cAMP-dependent protein kinase A (PKA). The results provide evidence for a new signal transduction pathway in which N-type Ca2+ channel modulation requires activation of Gs alpha but is independent of PKA-mediated phosphorylation.

Animals↗
PubMed1994

Modulation of Ca(2+)-channel currents by protein kinase C in adult rat sympathetic neurons.

1. Modulation of Ca(2+)-channel currents by phorbol-12-myristate-13-acetate (PMA) was investigated in acutely dissociated adult rat superior cervical ganglion neurons using the whole cell variant of the patch-clamp technique. 2. PMA (500 nM) increased the current amplitudes, accelerated the inactivation of step currents, retarded the deactivation of tail currents, and shifted the tail current activation to more negative potentials. 3. The effects of PMA were concentration and voltage dependent and mediated through activation of protein kinase C (PKC). PMA also increased Ca2+ currents recorded with the perforated patch technique. 4. PMA affected the N-type Ca2+ channels and an omega-conotoxin GVIA-resistant current component. Ca2+ currents affected by PMA were not sensitive to omega-agatoxin IVA or nimodipine. 5. PMA not only attenuated Ca(2+)-channel inhibition induced by alpha 2-adrenoceptor agonist, which modulates Ca2+ channels via a pertussis toxin (PTX)-sensitive pathway, but also attenuated current inhibition by vasoactive intestinal polypeptide, which modulates Ca2+ channels via a PTX-insensitive but cholera toxin-sensitive pathway. 6. PMA reversed Ca(2+)-channel inhibition induced by tonic activation of G-protein in the absence of neurotransmitter (even in neurons pretreated with PTX) or induced by activation of G-proteins with guanosine 5'-O-(3-thiotriphosphate) (GTP)-gamma-S. 7. Inhibition of phosphatase by okadaic acid or substitution of Ba2+ for Ca2+ in the external solutions accelerated the PMA effect. 8. Our results suggest that activation of PKC antagonizes G-protein mediated inhibition of Ca2+ channels by shifting Ca2+ channels from the "reluctant" state to the "willing" state. The G-proteins and, more likely, the N-type Ca2+ channels may be the target of PKC phosphorylation. Protein phosphatases may be involved in counteracting the PKC phosphorylation in rat sympathetic neurons.

Animals↗
PubMed1993

2,3-butanedione monoxime blockade of Ca2+ currents in adult rat sympathetic neurons does not involve 'chemical phosphatase' activity.

Effects of the 'chemical phosphatase' 2,3-butanedione monoxide (BDM) on voltage-activated Ca2+ currents of adult rat superior cervical ganglion neurons were investigated using the whole-cell patch-clamp technique. BDM produced a rapid (< 10 s), reversible and dose-dependent (IC50 = 18.3 mM) inhibition of Ca2+ currents. The action of BDM was not prevented by 1 mM 8-(4-chlorophenylthio)-cAMP or 50 microM isoproterenol. H-7, a non-specific protein kinase inhibitor at 200 microM, did not prevent the rapid recovery from BDM-induced inhibition. Our results suggest that BDM inhibition of Ca2+ currents in rat sympathetic neurons does not require a 'chemical phosphatase' activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Anomalous permeation of Na+ through a putative K+ channel in rat superior cervical ganglion neurones.

1. An unanticipated inward tail current was recorded from freshly isolated adult rat superior cervical ganglion (SCG) neurones using the whole-cell variant of the patch-clamp technique. The tail current was present when Na+ was substituted for tetraethylammonium (TEA) as the primary monovalent cation in external solutions designed to isolate Ca2+ channel currents (0.5 microM tetrodotoxin present and K+ omitted). 2. The tail current was observed following step potentials positive to -30 mV and reached half-activation near -9.0 mV. The decay of the tail current was voltage dependent and could be described with two time constants. Between potentials of -120 and -70 mV, tau f, the fast component, varied from 3 to 8 ms and tau s, the slow component, changed from 12 to 30 ms, respectively. 3. The tail current was not carried by Ca2+, and did not appear to flow through a voltage-gated Ca2+ channel or a Ca(2+)-dependent channel as it persisted in the absence of external Ca2+ or in the presence of the Ca2+ channel blocker, Cd2+ (0.1 mM). 4. Varying the external [Cl-] did not alter the reversal potential of the tail current indicating that Cl- was not the charge carrier. 5. The reversal potential of the tail current changed in accordance with the Nernst relationship when [Na+]i/[Na]o was altered. Our results suggested that this 'unusual or unanticipated current' (Iu) was carried primarily by Na+. 6. Iu was inhibited by the K+ channel-blocking agents quinidine (0.1 mM), external Ba2+ (5 mM) and internal Cs+ (145 mM). TEA (20 mM either internally or externally) and dendrotoxin (10 microM) were not effective inhibitors of Iu. 7. The decay time constants of the tail current and parameters of activation and inactivation of Iu were similar to those of TEA-insensitive delayed rectifier-type K+ channel currents observed in the presence of 145 mM external K+. 8. Iu was reduced in the presence of either external or internal K+. The interaction of external K+ with Na+ on the Iu tail amplitude was reminiscent of anomalous mole-fraction behaviour. 9. Ion permeability studies revealed that the channel producing Iu had a permeability sequence to monovalent cations of 3.5:2.5:2:1:0.5 for Rb+, K+, Cs+, Na+ and Li+, respectively. 10. These data suggest that in the absence of external K+, the ion selectivity of a TEA-insensitive K+ channel in sympathetic neurones is profoundly diminished. Under these conditions, Na+ traversing a K+ channel can generate an unanticipated inward current.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Adenosine modulates voltage-gated Ca2+ channels in adult rat sympathetic neurons.

1. Ca(2+)-channel modulation by adenosine was investigated in enzymatically dispersed adult rat superior cervical ganglion (SCG) neurons using the whole-cell variant of the patch-clamp technique. 2. Adenosine produced a concentration-dependent decrease in the Ca(2+)-current amplitude with an EC50 of 174 nM and maximum inhibition of 36%. The effects of adenosine on the Ca2+ current were both time and voltage dependent. The inhibition was maximal at +10 mV and decreased at either hyperpolarizing or depolarizing potentials. 3. The inhibitory response desensitized after prolonged (> 1 min) exposure to 10 microM adenosine, whereas multiple brief (< 30 s) applications slightly decreased the subsequent response. 4. Adenosine-induced Ca2+ current inhibition was mediated by an A1-type adenosine receptor, because the half-maximal inhibition value for an A1 receptor selective agonist, chloro-N-cyclopentyladenosine, was 1,000-fold lower than that for an A2 receptor selective agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarbozamido adenosine hydrochloride (33 nM vs. 40 microM, respectively). 5. A guanine nucleotide binding protein (G protein) appeared to be involved in the action of adenosine, because: 1) the adenosine-induced current inhibition could be largely relieved by depolarizing voltage prepulses; 2) tail current analysis revealed that adenosine shifted Ca(2+)-channel activation to more depolarized potentials; and 3) adenosine inhibition was abolished by 2 mM intracellular guanosine 5'-O-(2-thiodiphosphate) or 500 ng/ml pertussis toxin pretreatment. 6. Adenosine did not appear to inhibit L-type Ca2+ channels, because the prolonged tail current component induced by the dihydropyridine "agonist" 2,6-dimethy-3-carbomethoxy-5-nitro-4-(2-trifluoromethyl-phenyl)- 1,4-dihydropyridine (2 microM) was not affected by adenosine. 7. Adenosine-induced inhibition was reduced to approximately 15% after application of 10 microM omega-conotoxin GVIA, suggesting that adenosine primarily inhibits N-type Ca2+ channels. The Ca(2+)-current component resistant to omega-conotoxin GVIA was also resistant to omega-agatoxin IVA (200 nM), suggesting a lack of P-type of Ca2+ channels in SCG neurons. 8. In conclusion, adenosine produces a dose-, time-, and voltage-dependent inhibition of Ca2+ currents in SCG neurons. Adenosine acts on an A1 adenosine receptor subtype in SCG neurons via a pertussis toxin-sensitive G protein to inhibit N-type Ca2+ channels and an unidentified Ca(2+)-current component. Modulation of Ca2+ currents by adenosine may be an important mechanism for its inhibitory effect on neurotransmitter release in sympathetic neurons.

Adenosine↗