Lead (Pb2+) modulation of potassium currents of guinea pig outer hair cells

Abstract

Outer hair cells (OHC) are mechanosensitive sensory cells of the inner ear cochlea and are involved in modulating the activity of inner hair cells in the transduction of an acoustic stimulus. Potassium (K + ) currents play an important role in the sensory transduction process. K + currents were recorded from acutely dissociated OHC obtained from the guinea pig organ of Corti. The whole-cell patch clamp technique was employed. We identified a channel that exhibited outward current of the delayed rectifier type (Kv). Kv channels mediating inward currents carried by potassium ions were also identified and took on the appearance of a previously described inwardly rectifying current. Lead (Pb 2 + ) acetate at concentrations of 0.1, 1.0, 10, and 100 AM was bath applied. Time to activation for outward-going current was not affected by Pb 2 + . The time course of Pb 2 + effects was seen as a dose-dependent reduction of K + current over time, with very little or no recovery after washout. Pb 2 + inhibited the outward Kv relative current with values of 0.10, 0.14, 0.18, and 0.30 at 0.1, 1.0, 10, and 100 AM, respectively. Pb 2 + did not modulate time to activation, peak current, or inactivation of inward I K . The effects of Pb 2 + on the potassium currents of OHC are not remarkable and therefore OHC are probably not a major cause of purported peripheral hearing loss observed in Pb 2 + -exposed animals and humans. D

Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels

“…This result suggests that Pb 2+ blocks Cav1.2 channels, and, at higher doses, possibly K + channels as well. These results are consistent with previous reports using other cell types, and can explain the toxic actions of lead (Atchison 2003;Liang et al 2004;Madeja et al , 1997;Peng et al 2002;Yu et al 2003).…”

“…Lead ions have also been reported to reversibly inhibit delayed and transient outward potassium currents in hippocampal neurons (Madeja et al 1995(Madeja et al , 1997Yu et al 2003). These effects were found in both steady-state activation and inactivation experiments (Madeja et al 1997;Yu et al 2003); however, similar findings were not observed in Kv channels from outer hair cells (Liang et al 2004). In addition to the NMDA receptor, acute lead exposure has been reported to modify the action of other receptors by modifying their function and also reducing their expression levels during chronic exposures (Marchetti 2014;Vijverberg et al 1994b).…”

Environmental Lead Exposure and Otoacoustic Emissions in Andean Children

“…Other animal studies also found no significant Pb-related effects on the cochlea. Experimental studies using guinea pigs exposed to Pb, or in vitro experiments on dissociated guinea pig outer hair cells bathed in Pb acetate found no apparent morphological changes in the cochlea, no marked effects on the endocochlear potential or the cochlear microphonic response, and no significant effects on outer hair cell electromotility (the process leading to the generation of otoacoustic emissions) (Gozdzik-Zolnierkiewicz & Moszynski, 1969; Yamamura, et al, 1989; Tuncel, et al, 2002; Liang et al, 2004). Because the cochlear microphonic response (or receptor potential) is generated primarily by the outer hair cells of the inner ear, ototoxic effects should be manifested in both a diminished cochlear microphonic response and abnormal DPOAE, although DPOAE may be more hair cell place-specific than the cochlear microphonic.…”

Zinc Activates TREK-2 Potassium Channel Activity

“…Pb 2ϩ blocks voltage-gated Ca 2ϩ and K ϩ channels and hyperpolarization-activated channels but activates SK4, a Ca 2ϩ -activated K ϩ channel, by acting as a Ca 2ϩ surrogate. These findings suggest that Pb 2ϩ acts differently on different ion channels (Cao and Houamed, 1999;Atchison, 2003;Dai et al, 2003;Liang et al, 2004). Therefore, its effects may differ between different types of two-pore K ϩ channels.…”