Comparison of neuronal nicotinic receptors in rat sympathetic neurones with subunit pairs expressed in Xenopus oocytes.

Abstract

1. The agonist sensitivity of nicotinic acetylcholine receptors in rat superior cervical ganglion (SCG) neurones was compared with that of cloned receptors expressed in Xenopus oocytes by pairwise injections of a3-,B2 or a3-,B4 neuronal nicotinic subunit combinations. 2. Agonist responses in rat SCG neurones indicated that cytisine was the most potent agonist and lobeline the least potent (rank order of potency: cytisine > dimethylphenylpiperazinium iodide (DMPP) > nicotine > ACh > carbachol > lobeline). Deneris et al. 1991) and some (e.g. a7) form functional receptors homomerically (Seguela, Wadiche, Dineley-Miller, Dani & Patrick, 1993). Rat superior cervical ganglion (SCG) neurones express mRNAs for the a3, a7, /2 and /14 subunits of the nicotinic acetylcholine receptor, with conflicting information concerning the presence of a4-1 and a5 mRNAs (Rust, Burgunder, Lauterburg & Cachelin, 1994;Mandelzys, Pie, Deneris & Cooper, 1994), but it is not known which of these subunits co-assemble to form the native functional receptors. These receptors have been extensively studied and show a number of functional as well as structural differences from those found in muscle (reviewed by Role, 1992).One way to characterize receptor subtypes is by measuring the relative potencies of a series of agonists; for example, cytisine is a potent agonist, relative to acetylcholine, for a3-,B4 receptors, but very weak for a3-/12 receptors (Luetje & Patrick, 1991; and present work). In order to cast light on the nature of the native receptors in rat sympathetic neurones, we have made parallel measurements, under comparable conditions, of agonist potency ratios on (a) neurones of the rat superior cervical ganglion, and (b) AChRs expressed in Xenopus laevis oocytes using a3-/12 or a3-,/4 subunit pairs. These

Selective Modulation of Neuronal Nicotinic Acetylcholine Receptor Channel Subunits by Go-Protein Subunits

“…G-protein activation did not modify currents evoked by the cholinergic agonist, cytisine, which has been shown to be most potent for ␣3␤4 and ␣3␤4␣5 subunit combinations (Covernton et al, 1994). Furthermore, no direct interaction between the G o -protein subunits and the intracellular region of the ␤4 and ␣7 subunit was observed.…”

Linking Exponential Components to Kinetic States in Markov Models for Single-Channel Gating

“…The problem is further compounded because the methods used to calculate the exponential components from gating mechanisms give little practical information about the relationships between specifi c components and states. For analytic solutions, which can be derived for models with a limited number of states, the relationship between components and states is obscured in the equations, as shown in the Appendix and Covernton et al, (1994) for a three state model, and in Hawkes (1977, 1981 ), Magleby and Pallotta (1983) , and Jackson (1997) for more complex models. For the numeric methods that can be used to solve any gating mechanism Hawkes, 1981, 1982), there is even less practical information about the contributions of specifi c states to the various exponential components because of the matrix specifi c constituent distribution { C 1 -(C 2 -C 1 ) n } for n = 0 to effectively infi nity (see below) was simulated with N × (P C1-C2 ) n × P C1-O1 random intervals of duration …”

Deficiency of Nicotinic Acetylcholine Receptor β4 Subunit Causes Autonomic Cardiac and Intestinal Dysfunction

“…However, only 5 of the 12 nAChR subunits (␣3, ␣5, ␣7, ␤2, and ␤4) are known to exist in autonomic ganglia (Mandelzys et al, 1994;Zhou et al, 1998;Devay et al, 1999;Nelson and Lindstrom, 1999;Erkman et al, 2000), and they are not distributed homogenously (Covernton et al, 1994;Klimaschewski et al, 1994;Poth et al, 1997;Sivilotti et al, 1997). Different nAChR subunit combinations are spatially segregated from each other in discrete membrane microregions relative to synapses (Horch and Sargent, 1995;Poth et al, 1997;Shoop et al, 1999).…”