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.

Ingelman-Sundberg, Hanna (författare)
Dzabic, MensurKarolinska Institutet (författare)
Awasum, Justina (författare)
Nguyen, Khanh Hoa (författare)
Östenson, Claes-GöranKarolinska Institutet (författare)
Pierro, Cristina (författare)
Tedeschi, Patrizia (författare)
Woolcott, Orison (författare)
Chiounan, ShiueKarolinska Institutet (författare)
Lund, Per-Eric (författare)
Larsson, Olof (författare)
Islam, M. ShahidulKarolinska Institutet,Uppsala universitet,Medicin (författare)
Karolinska InstitutetMedicin (creator_code:org_t)

Av författaren/redakt...: Gustafsson, Aman ...; Ingelman-Sundber ...; Dzabic, Mensur; Awasum, Justina; Nguyen, Khanh Ho ...; Östenson, Claes- ...; visa fler...; Pierro, Cristina; Tedeschi, Patriz ...; Woolcott, Orison; Chiounan, Shiue; Lund, Per-Eric; Larsson, Olof; Islam, M. Shahid ...; visa färre...

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