Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones

A. Surprenant, Ke-Zhong Shen, R. A. North, H. Tatsumi

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Abstract

1. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 μM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by ω-conotoxin (100 nM), and unaffected by Bay K 8644 (0l1-10 μM) and nifedipine (1 μM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 μM for noradrenaline, 4 nM for somatostatin and 1 μM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current with 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were α2-adrenoceptors and δ-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-γ-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (G(o) or G(i)) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.

Original languageEnglish (US)
Pages (from-to)585-608
Number of pages24
JournalJournal of Physiology
Volume431
StatePublished - 1990

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Somatostatin
Opioid Analgesics
Norepinephrine
Guinea Pigs
Calcium
Neurons
Enkephalins
Cadmium
GTP-Binding Proteins
Conotoxins
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Guanosine 5'-O-(3-Thiotriphosphate)
Cesium
Whooping Cough
Pertussis Toxin
Opioid Receptors
Patch-Clamp Techniques
Nifedipine
Guanosine Triphosphate
Cobalt

ASJC Scopus subject areas

  • Physiology

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Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones. / Surprenant, A.; Shen, Ke-Zhong; North, R. A.; Tatsumi, H.

In: Journal of Physiology, Vol. 431, 1990, p. 585-608.

Research output: Contribution to journalArticle

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abstract = "1. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50{\%} block were 2.5, 500 and 2000 μM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by ω-conotoxin (100 nM), and unaffected by Bay K 8644 (0l1-10 μM) and nifedipine (1 μM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50{\%}; concentrations giving half-maximal inhibition were 5.5 μM for noradrenaline, 4 nM for somatostatin and 1 μM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current with 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were α2-adrenoceptors and δ-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-γ-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (G(o) or G(i)) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.",
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AU - Tatsumi, H.

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N2 - 1. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 μM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by ω-conotoxin (100 nM), and unaffected by Bay K 8644 (0l1-10 μM) and nifedipine (1 μM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 μM for noradrenaline, 4 nM for somatostatin and 1 μM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current with 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were α2-adrenoceptors and δ-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-γ-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (G(o) or G(i)) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.

AB - 1. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 μM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by ω-conotoxin (100 nM), and unaffected by Bay K 8644 (0l1-10 μM) and nifedipine (1 μM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 μM for noradrenaline, 4 nM for somatostatin and 1 μM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current with 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were α2-adrenoceptors and δ-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-γ-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (G(o) or G(i)) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.

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