Sensitivity to dihydropyridines, omega-conotoxin and noradrenaline reveals multiple high-voltage-activated Ca2+ channels in rat insulinoma and human pancreatic beta-cells

Pflugers Arch. 1993 Jun;423(5-6):462-71. doi: 10.1007/BF00374942.

Abstract

High-voltage-activated (HVA) Ba2+ currents of rat insulinoma (RINm5F) and human pancreatic beta-cells were tested for their sensitivity to dihydropyridines (DHPs), omega-conotoxin (omega-CgTx) and noradrenaline. In RINm5F cells, block of HVA currents by nimodipine, nitrendipine and nifedipine was voltage- and dose-dependent (apparent KD < 37 nM) and largely incomplete even at saturating doses of DHPs (mean 53%, at 10 microM and 0 mV). Analysis of slow tail currents in Bay K 8644-treated cells indicated the existence of Bay K 8644-insensitive channels that turned on at slightly more positive voltages and deactivated more quickly than Bay K 8644-modified channels. DHP Ca2+ agonists and antagonists in human beta-cells had similar features to RINm5F cells except that DHP block was more pronounced (76%, at 10 microM and 0 mV) and Bay K 8644 action was more effective, suggesting a higher density of L-type Ca2+ channels in these cells. In RINm5F cells, but not in human beta-cells, DHP-resistant currents were sensitive to omega-CgTx. The toxin depressed 10-20% of the DHP-resistant currents sparing a "residual" current (25-35%) with similar voltage-dependent characteristics and Ca2+/Ba2+ permeability. Noradrenaline (10 microM) exhibited different actions on the various HVA current components: (1) it prolonged the activation kinetics of omega-CgTx-sensitive currents, (2) it depressed by about 20% the size of DHP-sensitive currents, and (3) it had little or no effects on the residual DHP- and omega-CgTx-resistant current although intracellularly applied guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) prolonged its activation time course.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Barium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Dihydropyridines / pharmacology
  • Electrophysiology
  • Humans
  • Insulinoma / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Norepinephrine / pharmacology*
  • Pancreatic Neoplasms / metabolism*
  • Peptides / pharmacology
  • Rats
  • Tumor Cells, Cultured
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Dihydropyridines
  • Peptides
  • Barium
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • omega-Conotoxin GVIA
  • Norepinephrine