Ca2+ channel inhibition induced by nitric oxide in rat insulinoma RINm5F cells

Claudio Grassi, Marcello D'Ascenzo, Alessio Valente, Gian Battista Azzena

Research output: Contribution to journalArticlepeer-review


The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in insulin-secreting RINm5F cells was investigated using the patch- clamp technique in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 μM) induced a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The IC50 for SNP was 45 μM. A different NO donor, (±)S-nitroso-N-acetylpenicillamine (SNAP, 500 μM), also produced a 50% decrease in current amplitude. When 200 μM SNP was administered together with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1- oxyl-3-oxide (carboxy-PTIO, 300 μM), the Ba2+ current inhibition was lowered to 7%. Administration of 500 μM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP) mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current amplitude. When soluble guanylyl cyclase was blocked by 10 μM 1H-[1,2,41oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 μM SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of controls after the blockade of L- type Ca2+ channels and 30% in the presence of 2.5 μM ω-conotoxin-MVIIC. These data indicate that NO inhibits both L-type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the intracellular levels of cGMR. NO may then significantly influence the Ca2+-dependent release of hormones from secretory cells as well as that of neurotransmitters from nerve terminals.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Issue number2
Publication statusPublished - 1999


  • Ca channels
  • cGMP
  • Insulinoma
  • Nitric oxide
  • RINm5F cells
  • Sodium nitroprusside

ASJC Scopus subject areas

  • Physiology


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