Ryanodine receptor-operated activation of TRP-like channels can trigger critical Ca2+ signaling events in pancreatic beta-cells.
There is little information available concerning the link between the ryanodine (RY) receptors and the downstream Ca(2+) signaling events in beta-cells. In fura-2 loaded INS-1E cells, activation of RY receptors by 9-methyl 5,7-dibromoeudistomin D (MBED) caused a rapid rise of [Ca(2+)]i followed by a plateau and repetitive [Ca(2+)]i spikes on the plateau. The [Ca(2+)]i plateau was abolished by omission of extracellular Ca(2+) and by SKF 96365. In the presence of SKF 96365, MBED produced a transient increase of [Ca(2+)]i, which was abolished by thapsigargin. Activation of RY receptors caused Ca(2+) entry even when the ER Ca(2+) pool was depleted by thapsigargin. The [Ca(2+)]i plateau was not inhibited by nimodipine or ruthenium red, but was inhibited by membrane depolarization, La(3+), Gd(3+), niflumic acid, and 2-aminoethoxydiphenyl borate, agents that inhibit the transient receptor potential channels. The [Ca(2+)]i spikes were inhibited by nimodipine and ryanodine, indicating that they were due to Ca(2+) influx through the voltage-gated Ca(2+) channels and Ca(2+)-induced Ca(2+) release (CICR). Activation of RY receptors depolarized membrane potential as measured by patch clamp. Thus, activation of RY receptors leads to coherent changes in Ca(2+) signaling, which includes activation of TRP-like channels, membrane depolarization, activation of the voltage-gated Ca(2+) channels and CICR.
Gustafsson
Amanda Jabin
AJ
Department of Medicine, Karolinska Inst., Stockholm Söder Hospital, Stockholm 118 83, Sweden. amajab@ki.se
Ingelman-Sundberg
Hanna
H
Dzabic
Mensur
M
Awasum
Justina
J
Nguyen
Khanh Hoa
KH
Ostenson
Claes-Göran
CG
Pierro
Cristina
C
Tedeschi
Patrizia
P
Woolcott
Orison
O
Chiounan
Shiue
S
Lund
Per-Eric
PE
Larsson
Olof
O
Islam
Md Shahidul
MS
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D045744:Cell Line, Tumor; D007340:Insulinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel