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.
|Number of pages||11|
|Journal||Naunyn-Schmiedeberg's Archives of Pharmacology|
|Publication status||Published - 1999|
- calcium-activated chloride currents
- action potential after-depolarizations
- niflumic acid
- cultured sensory neurones
- ROOT GANGLION NEURONS
- CYCLIC ADP-RIBOSE
- INDUCED CALCIUM-RELEASE
- BULLFROG SYMPATHETIC NEURONS
- SENSORY NEURONS
- CA2+-DEPENDENT CURRENTS
- IONIC BASIS