The actions of ryanodine on Ca2+-activated conductances in rat cultured DRG neurones; evidence for Ca2+-induced Ca2+ release

A Ayar, R H Scott

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Abstract

The whole-cell recording technique was used to investigate the actions of a calcium release channel ligand, ryanodine, on calcium-activated chloride conductances, and to evaluate ryanodine-sensitive Ca2+-induced Ca2+ release from intracellular stores in cultured neonatal rat DRG neurones. The aim of the project was to use ryanodine as a pharmacological tool to evaluate calcium-induced calcium release in the cell bodies of cultured DRG neurones. Action potential after-depolarizations were attenuated by extracellular application of the chloride channel blocker, niflumic acid (10 mu M), and by ryanodine (10 mu M); these actions occurred without concurrent changes in evoked action potentials.

Ryanodine and caffeine (10 mM) activated calcium-dependent conductances and the responses to ryanodine were attenuated by depletion of caffeine-sensitive Ca2+ stores. The current clamp data were complicated by chang es in potassium conductances so studies were carried out under voltage clamp and voltage-activated calcium currents and calcium-activated chloride and non-selective cation currents were isolated pharmacologically Ryanodine (10 mu M) evoked delayed, inward, calcium-activated non-selective cation and chloride currents which reversed close to 0 mV and were attenuated by N-methyl-D-glucamine, niflumic acid and dantrolene. Consistent with actions on action potential after-depolarizations, niflumic acid (10 mu M) and ryanodine (10 mu M) attenuated calcium-activated chloride currents evoked by calcium entry through voltage-activated calcium channels. Niflumic acid and ryanodine had no effects on voltage-activated calcium currents evoked from a holding potential of -90 mV by voltage step commands to 0 mV.

In conclusion calcium-activated chloride conductances appear to be activated in part by calcium released from ryanodine-sensitive stores, and significant calcium-induced calcium release may occur locally in cell bodies of DRG neurones as a result of calcium entry through voltage-activated channels during an action potential.

Original languageEnglish
Pages (from-to)81-91
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume359
Publication statusPublished - 1999

Keywords

  • ryanodine
  • CICR
  • calcium-activated chloride currents
  • action potential after-depolarizations
  • niflumic acid
  • dantrolene
  • cultured sensory neurones
  • ROOT GANGLION NEURONS
  • CYCLIC ADP-RIBOSE
  • INDUCED CALCIUM-RELEASE
  • BULLFROG SYMPATHETIC NEURONS
  • SENSORY NEURONS
  • CA2+-DEPENDENT CURRENTS
  • IONIC BASIS
  • GUINEA-PIG
  • ACTIVATION
  • DEPOLARIZATION

Cite this

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title = "The actions of ryanodine on Ca2+-activated conductances in rat cultured DRG neurones; evidence for Ca2+-induced Ca2+ release",
abstract = "The whole-cell recording technique was used to investigate the actions of a calcium release channel ligand, ryanodine, on calcium-activated chloride conductances, and to evaluate ryanodine-sensitive Ca2+-induced Ca2+ release from intracellular stores in cultured neonatal rat DRG neurones. The aim of the project was to use ryanodine as a pharmacological tool to evaluate calcium-induced calcium release in the cell bodies of cultured DRG neurones. Action potential after-depolarizations were attenuated by extracellular application of the chloride channel blocker, niflumic acid (10 mu M), and by ryanodine (10 mu M); these actions occurred without concurrent changes in evoked action potentials.Ryanodine and caffeine (10 mM) activated calcium-dependent conductances and the responses to ryanodine were attenuated by depletion of caffeine-sensitive Ca2+ stores. The current clamp data were complicated by chang es in potassium conductances so studies were carried out under voltage clamp and voltage-activated calcium currents and calcium-activated chloride and non-selective cation currents were isolated pharmacologically Ryanodine (10 mu M) evoked delayed, inward, calcium-activated non-selective cation and chloride currents which reversed close to 0 mV and were attenuated by N-methyl-D-glucamine, niflumic acid and dantrolene. Consistent with actions on action potential after-depolarizations, niflumic acid (10 mu M) and ryanodine (10 mu M) attenuated calcium-activated chloride currents evoked by calcium entry through voltage-activated calcium channels. Niflumic acid and ryanodine had no effects on voltage-activated calcium currents evoked from a holding potential of -90 mV by voltage step commands to 0 mV.In conclusion calcium-activated chloride conductances appear to be activated in part by calcium released from ryanodine-sensitive stores, and significant calcium-induced calcium release may occur locally in cell bodies of DRG neurones as a result of calcium entry through voltage-activated channels during an action potential.",
keywords = "ryanodine, CICR, calcium-activated chloride currents, action potential after-depolarizations, niflumic acid, dantrolene, cultured sensory neurones, ROOT GANGLION NEURONS, CYCLIC ADP-RIBOSE, INDUCED CALCIUM-RELEASE, BULLFROG SYMPATHETIC NEURONS, SENSORY NEURONS, CA2+-DEPENDENT CURRENTS, IONIC BASIS, GUINEA-PIG, ACTIVATION, DEPOLARIZATION",
author = "A Ayar and Scott, {R H}",
year = "1999",
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pages = "81--91",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
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TY - JOUR

T1 - The actions of ryanodine on Ca2+-activated conductances in rat cultured DRG neurones; evidence for Ca2+-induced Ca2+ release

AU - Ayar, A

AU - Scott, R H

PY - 1999

Y1 - 1999

N2 - The whole-cell recording technique was used to investigate the actions of a calcium release channel ligand, ryanodine, on calcium-activated chloride conductances, and to evaluate ryanodine-sensitive Ca2+-induced Ca2+ release from intracellular stores in cultured neonatal rat DRG neurones. The aim of the project was to use ryanodine as a pharmacological tool to evaluate calcium-induced calcium release in the cell bodies of cultured DRG neurones. Action potential after-depolarizations were attenuated by extracellular application of the chloride channel blocker, niflumic acid (10 mu M), and by ryanodine (10 mu M); these actions occurred without concurrent changes in evoked action potentials.Ryanodine and caffeine (10 mM) activated calcium-dependent conductances and the responses to ryanodine were attenuated by depletion of caffeine-sensitive Ca2+ stores. The current clamp data were complicated by chang es in potassium conductances so studies were carried out under voltage clamp and voltage-activated calcium currents and calcium-activated chloride and non-selective cation currents were isolated pharmacologically Ryanodine (10 mu M) evoked delayed, inward, calcium-activated non-selective cation and chloride currents which reversed close to 0 mV and were attenuated by N-methyl-D-glucamine, niflumic acid and dantrolene. Consistent with actions on action potential after-depolarizations, niflumic acid (10 mu M) and ryanodine (10 mu M) attenuated calcium-activated chloride currents evoked by calcium entry through voltage-activated calcium channels. Niflumic acid and ryanodine had no effects on voltage-activated calcium currents evoked from a holding potential of -90 mV by voltage step commands to 0 mV.In conclusion calcium-activated chloride conductances appear to be activated in part by calcium released from ryanodine-sensitive stores, and significant calcium-induced calcium release may occur locally in cell bodies of DRG neurones as a result of calcium entry through voltage-activated channels during an action potential.

AB - The whole-cell recording technique was used to investigate the actions of a calcium release channel ligand, ryanodine, on calcium-activated chloride conductances, and to evaluate ryanodine-sensitive Ca2+-induced Ca2+ release from intracellular stores in cultured neonatal rat DRG neurones. The aim of the project was to use ryanodine as a pharmacological tool to evaluate calcium-induced calcium release in the cell bodies of cultured DRG neurones. Action potential after-depolarizations were attenuated by extracellular application of the chloride channel blocker, niflumic acid (10 mu M), and by ryanodine (10 mu M); these actions occurred without concurrent changes in evoked action potentials.Ryanodine and caffeine (10 mM) activated calcium-dependent conductances and the responses to ryanodine were attenuated by depletion of caffeine-sensitive Ca2+ stores. The current clamp data were complicated by chang es in potassium conductances so studies were carried out under voltage clamp and voltage-activated calcium currents and calcium-activated chloride and non-selective cation currents were isolated pharmacologically Ryanodine (10 mu M) evoked delayed, inward, calcium-activated non-selective cation and chloride currents which reversed close to 0 mV and were attenuated by N-methyl-D-glucamine, niflumic acid and dantrolene. Consistent with actions on action potential after-depolarizations, niflumic acid (10 mu M) and ryanodine (10 mu M) attenuated calcium-activated chloride currents evoked by calcium entry through voltage-activated calcium channels. Niflumic acid and ryanodine had no effects on voltage-activated calcium currents evoked from a holding potential of -90 mV by voltage step commands to 0 mV.In conclusion calcium-activated chloride conductances appear to be activated in part by calcium released from ryanodine-sensitive stores, and significant calcium-induced calcium release may occur locally in cell bodies of DRG neurones as a result of calcium entry through voltage-activated channels during an action potential.

KW - ryanodine

KW - CICR

KW - calcium-activated chloride currents

KW - action potential after-depolarizations

KW - niflumic acid

KW - dantrolene

KW - cultured sensory neurones

KW - ROOT GANGLION NEURONS

KW - CYCLIC ADP-RIBOSE

KW - INDUCED CALCIUM-RELEASE

KW - BULLFROG SYMPATHETIC NEURONS

KW - SENSORY NEURONS

KW - CA2+-DEPENDENT CURRENTS

KW - IONIC BASIS

KW - GUINEA-PIG

KW - ACTIVATION

KW - DEPOLARIZATION

M3 - Article

VL - 359

SP - 81

EP - 91

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

ER -