Effects of strontium on the permeation and gating phenotype of calcium channels in hair cells

Adrian Rodriguez-Contreras, Ping Lv, Jun Zhu, Jeong Kim Hyo, Ebenezer N. Yamoah

Research output: Contribution to journalArticle

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Abstract

To minimize the effects of Ca2+ buffering and signaling, this study sought to examine single Ca2+ channel properties using Sr 2+ 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 Sr 2+ 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.

Original languageEnglish (US)
Pages (from-to)2115-2124
Number of pages10
JournalJournal of Neurophysiology
Volume100
Issue number4
DOIs
StatePublished - Oct 2008

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Strontium
Calcium Channels
Ions
Phenotype
Membrane Potentials
Buffers
1,4-dihydropyridine

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Effects of strontium on the permeation and gating phenotype of calcium channels in hair cells. / Rodriguez-Contreras, Adrian; Lv, Ping; Zhu, Jun; Hyo, Jeong Kim; Yamoah, Ebenezer N.

In: Journal of Neurophysiology, Vol. 100, No. 4, 10.2008, p. 2115-2124.

Research output: Contribution to journalArticle

Rodriguez-Contreras, A, Lv, P, Zhu, J, Hyo, JK & Yamoah, EN 2008, 'Effects of strontium on the permeation and gating phenotype of calcium channels in hair cells', Journal of Neurophysiology, vol. 100, no. 4, pp. 2115-2124. https://doi.org/10.1152/jn.90473.2008
Rodriguez-Contreras, Adrian ; Lv, Ping ; Zhu, Jun ; Hyo, Jeong Kim ; Yamoah, Ebenezer N. / Effects of strontium on the permeation and gating phenotype of calcium channels in hair cells. In: Journal of Neurophysiology. 2008 ; Vol. 100, No. 4. pp. 2115-2124.
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AB - To minimize the effects of Ca2+ buffering and signaling, this study sought to examine single Ca2+ channel properties using Sr 2+ 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 Sr 2+ 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.

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