Neuronal endoplasmic reticulum acts as a single functional Ca2+ store shared by ryanodine and inositol-1,4,5-trisphosphate receptors as revealed by intra-ER [Ca2+] recordings in single rat sensory neurones.
We addressed the fundamentally important question of functional continuity of endoplasmic reticulum (ER) Ca(2+) store in nerve cells. In cultured rat dorsal root ganglion neurones we measured dynamic changes in free Ca(2+) concentration within the ER lumen ([Ca(2+)](L)) in response to activation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs). We found that both receptors co-exist in these neurones and their activation results in Ca(2+) release from the ER as judged by a decrease in [Ca(2+)](L). Depletion of Ca(2+) stores following an inhibition of sarco(endoplasmic)reticulum Ca(2+)-ATPase by thapsigargin or cyclopiazonic acid completely eliminated Ca(2+) release via both InsP(3)Rs and RyRs. Similarly, when the store was depleted by continuous activation of InsP(3)Rs, activation of RyRs (by caffeine or 0.5 microM ryanodine) failed to produce Ca(2+) release, and vice versa, when the stores were depleted by activators of RyRs, the InsP(3)-induced Ca(2+) release disappeared. We conclude that in mammalian neurones InsP(3)Rs and RyRs share the common continuous Ca(2+) pool associated with ER.
Solovyova
Natasha
N
The University of Manchester, School of Biological Sciences, 1.124 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
Verkhratsky
Alexei
A
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D010726:Phosphodiesterase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid