MULTIPLE EFFECTS OF NORDIHYDROGUAIARETIC ACID ON IONIC CURRENTS IN RAT ISOLATED TYPE-I CAROTID-BODY CELLS

1 The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were inv estigated by use of whole-cell and outside-out patch clamp techniques. 2 NDGA (5-50 mu M) produced a concentration-dependent inhibition of w hole-cell K+ currents at all activating test potentials (holding poten tial -70 mV). The time-course of the inhibition was also concentration -dependent and the effects of NDGA were only reversible following brie f periods of exposure (<2 min). Another lipoxygenase inhibitor, phenid one (5 mu M), was without effect on whole-cell K+ currents in carotid body type I cells. 3 NDGA (5-50 mu M) also inhibited whole-cell Ca2+ c hannel currents (recorded with Ba2+ as charge carrier) in a concentrat ion-dependent manner. 4 Isolation of voltage-gated K+ channels by use of high [Mg2+] (6 mM), low [Ca2+] (0.1 mM) solutions revealed a direct inhibition of the voltage-sensitive component of the whole-cell K+ cu rrent by NDGA (50 mu M). 5 In excised, outside-out patches NDGA (20-50 mu M) increased large conductance, Ca2+ activated K+ channel activity approximately 10 fold, an effect which could be reversed by either te traethylammonium (10 mM) or charybdotoxin (30 nM). 6 It is concluded t hat NDGA activates maxi-K+ channels in carotid body type I cells and o ver the same concentration range inhibits voltage-sensitive K+ and Ca2 + channels. The inhibition of whole cell K+ currents seen is most like ly due to a combination of direct inhibition of the voltage-sensitive K+ current and indirect inhibition of maxi-K+ channel activity through blockade of Ca2+ channels.