Block of non-L-, non-N-type Ca2+ channels in rat insulinoma RINm5F cells by omega-agatoxin IVA and omega-conotoxin MVIIC.
The high-voltage-activated (HVA) Ba2+ currents of rat insulinoma RINm5F cells insensitive to dihydropyridines (DHP) and omega-conotoxin GVIA (omega-CTx-GVIA) have been studied for their sensitivity to omega-agatoxin-IVA (omega-Aga-IVA) and omega-CTx-MVIIC. Blockade of HVA currents by omega-Aga-IVA was partial (mean 24%), reversible and saturated around 350 nM (half block approximately 60 nM). Blockade by omega-CTx-MVIIC was more potent (mean 45%), partly irreversible and saturated above 3 microM. The effects of both toxins were additive with that of nifedipine (5 microM) and were more pronounced at positive potentials. omega-Aga-IVA action was additive with that of omega-CTx-GVIA (3 microM) but was largely prevented by cell pre-treatment with omega-CTx-MVIIC (3 microM). In contrast, omega-CTx-MVIIC block was attenuated by omega-CTx-GVIA treatment (approximately 15%), suggesting that omega-CTx-MVIIC blocks the N-type (approximately 15%) and the non-L-, non-N-type channel sensitive to omega-Aga-IVA (approximately 30%). Consistent with this, cells deprived of most non-L-type channels by pre-incubation with omega-CTx-GVIA and omega-CTx-MVIIC exhibited predominant L-type currents that activated at more negative potentials than in normal cells (-30 mV in 5 mM Ba2+) and were effectively depressed by nifedipine (maximal block of 95% from -30 mV to +40 mV). Our results suggest that, besides L- and N-type channels, insulin-secreting RINm5F cells possess also a non-L-, non-N-type channel that contributes significantly to the total current (approximately 30%). Although the pharmacology of this channel is similar to Q-type and alpha 1 class A channels, its range of activation (> -20 mV) and its slow inactivation time course resemble more that of N- and P-type channels. The channel is therefore referred to as "Q-like".
Magnelli
V
V
Dip. Anatomia e Fisiologia Umana, Turin, Italy.
Pollo
A
A
Sher
E
E
Carbone
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004558:Electric Stimulation; D007340:Insulinoma / Q000378:metabolism*; D007700:Kinetics; D009543:Nifedipine / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C038806:1,4-dihydropyridine; D009543:Nifedipine