Calcium permeability and modulation of nicotinic acetylcholine receptor-channels in rat parasympathetic neurons

Authors

David J. Adams, University of MiamiFollow
Thomas J. Nutter, University of Miami

RIS ID

106179

Publication Details

Adams, D. J. & Nutter, T. J. (1992). Calcium permeability and modulation of nicotinic acetylcholine receptor-channels in rat parasympathetic neurons. Journal of Physiology (Paris), 86 (1-3), 67-76.

Abstract

Neuronal nicotinic acetylcholine (ACh)-activated currents in rat parasympathetic ganglion cells were examined using whole-cell and single-channel patch clamp recording techniques. The whole-cell current-voltage (I-V) relationship exhibited strong inward rectification and a reversal (zero current) potential of -3.9 mV in nearly symmetrical Na+ solutions (external 140 mM Na+/internal 160 mM Na+). Isosmotic replacement of extracellular Na+ with either Ca2+ or Mg2+ yielded the permeability (PX/PNa) sequence Mg2+ (1.1) > Na+ (1.0) > Ca2+ (0.65). Whole-cell ACh-induced current amplitude decreased as [Ca2+]0 was raised from 2.5 mM to 20 mM, and remained constant at higher [Ca2+]0. Unitary ACh-activated currents recorded in excised outside-out patches had conductances ranging from 15-35 pS with at least three distinct conductance levels (33 pS, 26 pS, 19 pS) observed in most patches. The neuronal nicotinic ACh receptor-channel had a slope conductance of 30 pS in Na+ external solution, which decreased to 20 pS in isotonic Ca2+ and was unchanged by isosmotic replacement of Na+ with Mg2+. ACh-activated single channel currents had an apparent mean open time (τ0) of 1.15 ± 0.16 ms and a mean burst length (τb) of 6.83 ± 1.76 ms at -60 mV in Na+ external solution. Ca2+-free external solutions, or raising [Ca2+]0 to 50-100 mM decreased both the τ0 and τb of the nAChR channel. Varying [Ca2+]0 produced a marked decrease in NP0, while substitution of Mg2+ for Na+ increased NP0. These data suggest that activation of the neuronal nAChR channel permits a substantial Ca2+ influx which may modulate Ca2+-dependent ion channels and second messenger pathways to affect neuronal excitability in parasympathetic ganglia.