BLOCK OF NON-L-TYPE, NON-N-TYPE CA2-AGATOXIN IVA AND OMEGA-CONOTOXIN MVIIC( CHANNELS IN RAT INSULINOMA RINM5F CELLS BY OMEGA)

The high-voltage-activated (HVA) Ba2+ currents of rat insulinoma RINm5 F cells insensitive to dihydropyridines (DHP) and omega-conotoxin GVIA (omega-CTx-GVIA) have been studied for their sensitivity to omega-aga toxin-IVA (omega-Aga-IVA) and omega-CTx-MVIIC. Blockade of HVA current s by omega-Aga-IVA was partial (mean 24%), reversible and saturated ar ound 350 nM (half block approximate to 60 nM). Blockade by omega-CTx-M VIIC was more potent (mean 45%), partly irreversible and saturated abo ve 3 mu M The effects of both toxins were additive with that of nifedi pine (5 mu M) and were more pronounced at positive potentials. omega-A ga-IVA action was additive with that of omega-CTx-GVIA (3 mu M) but wa s largely prevented by cell pre-treatment with omega-CTx-MVIIC (3 mu M ). In contrast, omega-CTx-MVIIC block was attenuated by omega-CTx-GVIA treatment (approximate to 15%), suggesting that omega-CTx-MVIIC block s the N-type (approximate to 15%) and the non-L-, non-N-type channel s ensitive to omega-Aga-IVA (approximate to 30%). Consistent with this, cells deprived of most non-L-type channels by pre-incubation with omeg a-CTx-GVIA and omega-CTx-MVIIC exhibited predominant L-type currents t hat activated at more negative potentials than in normal cells (-30 mV in 5 mM Ba2+) and were effectively depressed by nifedipine (maximal b lock 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 (approximate to 30%). Although the pharmacology of this chann el is similar to Q-type and alpha(1) class A channels, its range of ac tivation (> -20 mV) and its slow inactivation time course resemble mor e that of N- and P-type channels. The channel is therefore referred to as ''Q-like''.