Chemosensing at the carotid body. Involvement of a HERG-like potassium current in glomus cells.
Currently, it is not clear what type of K+ channel(s) is active at the resting membrane potential (RMP) in glomus cells of the carotid body (CB). HERG channels produce currents that are known to contribute to the RMP in other neuronal cells. The goal of the present study was to determine whether CB glomus cells express HERG-like (HL) K+ current, and if so, to determine whether HL currents regulate the RMP. With high [K+]o, depolarizing voltage steps from -85 mV revealed a slowly deactivating inward tail current indicative of HL K+ current in whole-cell, voltage clamped glomus cells. The HL currents were blocked by dofetilide (DOF) in a concentration-dependent manner (IC50 = 13 nM) and high concentrations (1 and 10 mM) of Ba2+. The steady-state activation properties of the HL current (Vh = -45 mV) suggest that it is active at the RMP in glomus cells. Whole-cell, current clamped glomus cells exhibited a RMP of -48 mV. 150 nM DOF caused a significant (14 mV) depolarizing shift in the RMP. In isolated glomus cells, [Ca2+]i increased in response to DOF (1 microM). In an in-vitro CB preparation, DOF increased basal sensory discharge in a concentration-dependent manner and significantly attenuated the sensory response to hypoxia. These results suggest that the HERG-like current is responsible for controlling the RMP in glomus cells of the rabbit CB, and that it is involved in the chemosensory response to hypoxia of the CB.
Overholt
J L
JL
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970, USA.
Ficker
E
E
Yang
T
T
Shams
H
H
Bright
G R
GR
Prabhakar
N R
NR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D027682:Cation Transport Proteins; D015687:Cell Hypoxia / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D051638:Ether-A-Go-Go Potassium Channels; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C063533:dofetilide; D002118:Calcium