Contribution of TASK-like potassium channels to the enhanced rat carotid body responsiveness to hypoxia.
A major hallmark of obstructive sleep apnea is the potentiation of the carotid body (CB) chemosensory response to acute hypoxia, as result of the chronic intermittent hypoxia (CIH) exposition. Several mechanisms have been involved in this CB chemosensory potentiation, but the primary target of CIH remains elusive. In physiological conditions, hypoxia depolarized CB chemoreceptor cells, trigger an increase of intracellular Ca(2+), and the subsequent transmitter's release. Since the depolarization is initiated by the inhibition of a TASK-like K(+) channel, we studied if CIH may increase the amplitude of the hypoxic-induced depolarization in the chemoreceptor cells, due to an enhanced inhibition of the TASK-like current.CBs obtained from adult rats exposed to CIH (5% O2, 12 times/hr for 8 hr/day) for 7 days were acute dissociated, and the membrane potential and TASK-like current were recorded from isolated chemoreceptor cells. Resting membrane properties were not modified by CIH, but the amplitude of the hypoxic-evoked depolarization increases ∼2-fold. The same result was obtained when all the voltage-dependent K(+) currents were pharmacologically blocked. Accordingly, the inhibition of the TASK-like current induced by acute hypoxia (PO(2) ∼5 torr) increased from ∼62% in control cells to ∼96% in the CIH cells.Present results show that acute hypoxic inhibition of TASK-like K(+) channel is potentiated by CIH exposure, suggesting that the enhancing effect of CIH on CB chemosensory responsiveness to hypoxia occurs at the initial step of the oxygen transduction in the CB chemoreceptor cells.
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. radelrio@uc.cl
Fernando C
FC
Ortiz
Rodrigo
R
Del Rio
Rodrigo
R
Varas
Rodrigo
R
Iturriaga
D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3