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

摘要

class="enumerated" style="list-style-type:decimal">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.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 (<2 min). Another lipoxygenase inhibitor, phenidone (5 μM), was without effect on whole-cell K⁺ currents in carotid body type I cells.NDGA (5–50 μM) also inhibited whole-cell Ca²⁺ channel currents (recorded with Ba²⁺ as charge carrier) in a concentration-dependent manner.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).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).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.