Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells

Abstract

ϩ currents that inhibit hypoxia-induced depolarization and that a decrease in this current with age could underlie, in part, the developmental increase in type I cell depolarization response to hypoxia. In dissociated type I cells from 0-to 1-and 11-to 16-day-old rats, using perforated patch-clamp and 70 mM K ϩ extracellular solution, we measured repolarization-induced inward K ϩ tail currents in the absence and presence of E-4031, a specific HERG channel blocker. This allowed isolation of the E-4031-sensitive HERG-like current. E-4031-sensitive peak currents in type I cells from 0-to-1-day-old rats were 2.5-fold larger than in cells from 11-to 16-day-old rats. E-4031-sensitive current density in newborn type I cells was twofold greater than in cells from 11-to 16-day-old rats. Under current clamp conditions, E-4031 enhanced hypoxia-induced depolarization in type I cells from 0-to-1-day-old but not 11-to 16-day-old rats. With use of fura 2 to measure intracellular Ca 2ϩ , E-4031 increased the cytosolic Ca 2ϩ concentration response to anoxia in cells from 0-to-1-day-old but not cells from 11-to 16-day-old rats. E-4031-sensitive K ϩ currents are present in newborn carotid body type I cells and decline with age. These findings are consistent with a role for E-4031-sensitive K ϩ current, and possibly HERG-like K ϩ currents, in the type I cell hypoxia response maturation.human ether-a-go-go-related gene; potassium channel; hypoxia THE CAROTID BODY chemoreceptors mediate ventilatory and other defensive responses to hypoxic stress in mammals (11,23,28) and appear to be important for survival during postnatal maturation (14,21,28). Despite their importance, the carotid chemoreceptors in neonates exhibit low sensitivity to hypoxia compared with adults and become more sensitive over the first few weeks of life. This process, termed "resetting" of carotid body O 2 sensitivity, occurs in all mammalian species studied to date (8,9,12,20,29,36,37

hERG K+Channels: Structure, Function, and Clinical Significance

“…In carotid sinus nerve preparations, dofetilide was also able to increase the basal sensory discharge. I Kr has also been demonstrated in rat carotid body chemoreceptor cells (326). The current density in these cells decreases with age, and this could be implicated in increased sensitivity to hypoxia during maturation.…”

K+ channels in O2 sensing and postnatal development of carotid body glomus cell response to hypoxia

“…HERG is also expressed in rat glomus cells, as judged by the inhibition of the outward K + current by E-4301, a specific blocker of HERG (Kim et al , 2005). In our own studies in cell-attached patches from rat glomus cells, opening of a small conductance K + channel (~12-pS) with long openings was observed.…”

“…Interestingly, the HERG current as determined from the E4301-sensitive current density was ~2-fold larger in glomus cells isolated from newborn rats than that from 11–16 day-old rats (Kim et al , 2005). E4301 produced a small depolarization (2.2–2.7 mV) of glomus cells from both age groups, indicating that the contribution of HERG to the background K + conductance is relatively small regardless of age.…”

Carotid chemoreceptor “resetting” revisited

“…Briefly, we used the HERG channel blocker E-4031 to study its role in CB glomus cells from P0-1 vs. P11-16 rats. E-4031 resulted in an increased depolarization response as well as [Ca 2+ ] i response to hypoxia in glomus cells from newborn but not mature rats, suggesting that HERG-like currents were damping newborn, but not mature glomus cell responses (Kim et al, 2005). The effect was modest, suggesting that HERG-like currents may play a small role in glomus cell functional development.…”