Multiple effects of nordihydroguaiaretic acid on ionic currents in rat isolated type I carotid body cells

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Abstract
2 The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were investigated by use of whole‐cell and outside‐out patch clamp techniques. 3 NDGA (5–50 μM) produced a concentration‐dependent inhibition of whole‐cell K+ currents at all activating test potentials (holding potential −70 mV). The time‐course of the inhibition was also concentration‐dependent and the effects of NDGA were only reversible following brief periods of exposure (+ currents in carotid body type I cells. 4 NDGA (5–50 μM) also inhibited whole‐cell Ca2+ channel currents (recorded with Ba2+ as charge carrier) in a concentration‐dependent manner. 5 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+ current by NDGA (50 μM). 6 In excised, outside‐out patches NDGA (20–50 μM) increased large conductance, Ca2+ activated K+ channel activity approximately 10 fold, an effect which could be reversed by either tetraethylammonium (10 mM) or charybdotoxin (30 nM). 7 It is concluded that NDGA activates maxi‐K+ channels in carotid body type I cells and over the same concentration range inhibits voltage‐sensitive K+ and Ca2+ channels. The inhibition of whole cell K+ currents seen is most likely 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. British Journal of Pharmacology (1997) 122, 923–929; doi:10.1038/sj.bjp.0701452