Zinc potentiates neuronal nicotinic receptors by increasing burst duration

Bernard Hsiao, Karla B. Mihalak, Karl Magleby, Charles W Luetje

Research output: Contribution to journalArticle

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Abstract

Micromolar zinc potentiates neuronal nicotinic acetylcholine receptors (nAChRs) in a subtype-dependent manner. Zinc potentiates receptor function even at saturating agonist concentrations, without altering the receptor desensitization rate. Potentiation could occur through an increase in the number of available receptors, an increase in single-channel current amplitude, or an increase in single-channel open probability. To distinguish among these possibilities, we examined rat neuronal nAChRs expressed in Xenopus oocytes. Blockade of a large fraction of ACh activated α4β4 or α4β2 receptors by the open channel blocker hexamethonium failed to change the extent of potentiation by zinc, suggesting that zinc does not change the number of available receptors. The single-channel amplitudes of ACh (1 μM) activated α4β4 receptors in outside-out patches were similar in the absence and the presence of 100 μM zinc (3.0 ± 0.1 and 2.9 ± 0.1 pA, respectively). To determine the effect of zinc on single-channel open probability, we examined α4β4 receptors in cell-attached patches. The open probability at 100 nM ACh (0.011 ± 0.002) was increased 4.5-fold by 100 μM zinc (0.050 ± 0.008), accounting for most of the potentiation observed at the whole cell level. The increase in open probability was due to an increase in burst duration, which increased from 207 ± 38 ms in the absence of zinc to 830 ± 189 ms in the presence of zinc. Our results suggest that potentiation of neuronal nAChRs by zinc is due to a stabilization of the bursting states of the receptor.

Original languageEnglish
Pages (from-to)999-1007
Number of pages9
JournalJournal of Neurophysiology
Volume99
Issue number2
DOIs
StatePublished - Feb 1 2008

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Nicotinic Receptors
Zinc
Hexamethonium
Xenopus
Oocytes

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Zinc potentiates neuronal nicotinic receptors by increasing burst duration. / Hsiao, Bernard; Mihalak, Karla B.; Magleby, Karl; Luetje, Charles W.

In: Journal of Neurophysiology, Vol. 99, No. 2, 01.02.2008, p. 999-1007.

Research output: Contribution to journalArticle

Hsiao, Bernard ; Mihalak, Karla B. ; Magleby, Karl ; Luetje, Charles W. / Zinc potentiates neuronal nicotinic receptors by increasing burst duration. In: Journal of Neurophysiology. 2008 ; Vol. 99, No. 2. pp. 999-1007.
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