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J Neurophysiol 100: 2115-2124, 2008. First published August 13, 2008; doi:10.1152/jn.90473.2008
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Effects of Strontium on the Permeation and Gating Phenotype of Calcium Channels in Hair Cells

Adrian Rodriguez-Contreras1, Ping Lv1, Jun Zhu1,2, Hyo Jeong Kim1 and Ebenezer N. Yamoah1

1Center for Neuroscience, Program in Communication Sciences, University of California, Davis, California; and 2Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, China

Submitted 15 April 2008; accepted in final form 30 July 2008

To minimize the effects of Ca2+ buffering and signaling, this study sought to examine single Ca2+ channel properties using Sr2+ ions, which substitute well for Ca2+ but bind weakly to intracellular Ca2+ buffers. Two single-channel fluctuations were distinguished by their sensitivity to dihydropyridine agonist (L-type) and insensitivity toward dihydropyridine antagonist (non-L-type). The L- and non-L-type single channels were observed with single-channel conductances of 16 and 19 pS at 70 mM Sr2+ and 11 and 13 pS at 5 mM Sr2+, respectively. We obtained KD estimates of 5.2 and 1.9 mM for Sr2+ for L- and non-L-type channels, respectively. At Ca2+ concentration of ~2 mM, the single-channel conductances of Sr2+ for the L-type channel was ~1.5 and 4.0 pS for the non-L-type channels. Thus the limits of single-channel microdomain at the membrane potential of a hair cell (e.g., –65 mV) for Sr2+ ranges from 800 to 2,000 ion/ms, assuming an ECa of 100 mV. The channels are ≥4-fold more sensitive at the physiological concentration ranges than at concentrations >10 mM. Additionally, the channels have the propensity to dwell in the closed state at high concentrations of Sr2+, which is reflected in the time constant of the first latency distributions. It is concluded that the concentration of the permeant ion modulates the gating of hair cell Ca2+ channels. Finally, the closed state/s that is/are altered by high concentrations of Sr2+ may represent divalent ion-dependent inactivation of the L-type channel.


Address for reprint requests and other correspondence: E. N. Yamoah, Ctr. for Neuroscience, Program in Communication Science, Univ. of California, Davis, 1544 Newton Ct., Davis, CA 95618 (E-mail: enyamoah{at}ucdavis.edu)







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