Evaluation of Ca2+ permeability of nicotinic acetylcholine receptors in hypothalamic histaminergic neurons

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Abstract

Hypothalamic histaminergic tuberomammillary (TM) neurons express nicotinic acetylcholine receptors (nAChRs) with kinetic and pharmacological properties resembling those of highly Ca2+ permeable α7 nAChRs. However, the Ca2+ permeability of TM nAChR channels has not been determined. To directly evaluate the Ca2+ permeability of TM nAChRs, patch-clamp recordings were conducted using non-cultured acutely dissociated TM neurons and external solutions containing low (2 mM) and high (20 mM) concentrations of Ca2+. A shift in the reversal potentials was determined from the current-voltage relationships and the permeability ratio, PCa/P Na, was estimated within the Goldman-Hodgkin-Katz constant field approximation. TM nAChRs were found to be highly Ca2+ permeable with the permeability ratio, PCa/PNa(nAChR) being ∼5.9 and the fractional Ca2+ current, Pf(nAChR) being ∼10.1% at -60 mV. As a positive control for the applied methods and analysis, the permeability ratio, PCa/PNa(NMDAR) being ∼8.3 and the fractional Ca2+ current, Pf(NMDAR) being ∼13.6 at -60 mV for NMDA receptors were determined using non-cultured acutely dissociated hippocampal pyramidal neurons and found similar to previously reported values. Therefore, these results demonstrate that native TM nAChRs are highly Ca 2+ permeable, but ∼1.4 fold less permeable to Ca2+ than native hippocampal pyramidal NMDA receptors.

Original languageEnglish
Pages (from-to)8-20
Number of pages13
JournalActa Biochimica et Biophysica Sinica
Volume42
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Alpha7
  • Calcium
  • Hypothalamic
  • NAChR
  • Permeability

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