Ryanodine receptor-operated activation of TRP-like channels can trigger critical Ca2+ signaling events in pancreatic beta-cells

• Published in: The FASEB journal Vol. 19; no. 2; p. 301
• Main Authors: Gustafsson, Amanda Jabin, Ingelman-Sundberg, Hanna, Dzabic, Mensur, Awasum, Justina, Nguyen, Khanh Hoa, Ostenson, Claes-Göran, Pierro, Cristina, Tedeschi, Patrizia, Woolcott, Orison, Chiounan, Shiue, Lund, Per-Eric, Larsson, Olof, Islam, Md Shahidul
• Format: Journal Article
• Language: English
• Published: United States 01.02.2005
• Subjects: Animals; Calcium Channels - metabolism; Calcium Signaling - physiology; Cell Line, Tumor; Insulinoma - chemistry; Insulinoma - metabolism; Insulinoma - pathology; Islets of Langerhans - chemistry; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Pancreatic Neoplasms - chemistry; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Patch-Clamp Techniques - methods; Rats; Rats, Wistar; Ryanodine Receptor Calcium Release Channel - metabolism
• ISSN: 1530-6860
• DOI: 10.1096/fj.04-2621fje

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.