HERG-like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body

Direct evidence for a specific K+ channel underlying the resting membrane p otential in glomus cells of the carotid body has been absent. The product o f the human ether-a-go-go-related gene (HERG) produces inward rectifier cur rents that are known to contribute to the resting membrane potential in oth er neuronal cells. The goal of the present study was to determine whether c arotid body glomus cells express HERG-like K+ current, and if so, to determ ine whether a HERG-like current regulates the resting membrane potential. F reshly dissociated rabbit glomus cells under whole cell voltage clamp exhib ited slowly decaying outward currents that activated 20-30 mV positive to t he resting membrane potential. Raising extracellular K+ revealed a slowly d eactivating inward tail current indicative of HERG-like K+ current. HERG-li ke currents were not found in cells resembling type LI cells. The HERG-like current was blocked by dofetilide (DOF) in a concentration-dependent manne r (IC50 = 13 +/- 4 nM, mean +/- SE) and high concentrations of Ba2+ (I and 10 mM). The biophysical and pharmacological characteristics of this inward tail current suggest that it is conducted by a HERG-like channel. The stead y-state activation properties of the HERG-like current (V-h = -44 +/- 2 mV) suggest that it is active at the resting membrane potential in glomus cell s. In whole cell, current-clamped glomus cells (average resting membrane po tential, - 48 +/- 4 mV), DOF, but not tetraethylammonium, caused a signific ant (13 mV) depolarizing shift in the resting membrane potential. Using flu orescence imaging, DOF increased [Ca2+](i) in isolated glomus cells. In an in-vitro carotid body preparation, DOF increased basal sensory discharge in the carotid sinus nerve in a concentration-dependent manner. These results demonstrate that glomus cells express a HERG-like current that is active a t, and responsible for controlling the resting membrane potential.