SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

G-protein-gated TRP-like cationic channel activated by muscarinic receptors: Effect of potential on single-channel gating

Zholos, AV; Zholos, AA; Bolton, TB (2004) G-protein-gated TRP-like cationic channel activated by muscarinic receptors: Effect of potential on single-channel gating. JOURNAL OF GENERAL PHYSIOLOGY, 123 (5). 581 - 598. ISSN 0022-1295 https://doi.org/10.1085/jgp.200309002
SGUL Authors: Bolton, Thomas Bruce

[img]
Preview
["document_typename_cannot open `/data/SGUL/sgul/eprints3/archives/sgul/documents/disk0/00/10/71/80/01/J' (No such file or directory) cannot open `Gen' (No such file or directory) cannot open `Physiol-2004-Zholos-581-98.pdf' (No such file or directory)" not defined] Published Version
Available under License St George's repository terms & conditions.

Download (2MB) | Preview

Abstract

There is little information about the mechanisms by which G-protein–coupled receptors gate ion channels although many ionotropic receptors are well studied. We have investigated gating of the muscarinic cationic channel, which mediates the excitatory effect of acetylcholine in smooth muscles, and proposed a scheme consisting of four pairs of closed and open states. Channel kinetics appeared to be the same in cell-attached or outside-out patches whether the channel was activated by carbachol application or by intracellular dialysis with GTPγS. Since in the latter case G-proteins are permanently active, it is concluded that the cationic channel is the major determinant of its own gating, similarly to the KACh channel (Ivanova-Nikolova, T.T., and G.E. Breitwieser. 1997. J. Gen. Physiol. 109:245–253). Analysis of adjacent-state dwell times revealed connections between the states that showed features conserved among many other ligand-gated ion channels (e.g., nAChR, BKCa channel). Open probability (PO) of the cationic channel was increased by membrane depolarization consistent with the prominent U-shaped I-V relationship of the muscarinic whole-cell current at negative potentials. Membrane potential affected transitions within each closed-open state pair but had little effect on transitions between pairs; thus, the latter are likely to be caused by interactions of the channel with its ligands, e.g., Ca2+ and Gαo-GTP. Channel activity was highly heterogeneous, as was evident from the prominent cycling behavior when PO was measured over 5-s intervals. This was related to the variable frequency of openings (as in the KACh channel) and, especially, to the number of long openings between consecutive long shuttings. Analysis of the underlying Markov chain in terms of probabilities allowed us to evaluate the contribution of each open state to the integral current (from shortest to longest open state: 0.1, 3, 24, and 73%) as PO increased 525-fold in three stages.

Item Type: Article
Additional Information: Copyright © 2004, The Rockefeller University Press RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.
Keywords: Animals, Calcium Channels, Calcium Signaling, Carbachol, Cells, Cultured, GTP-Binding Proteins, Guinea Pigs, Ileum, Ion Channel Gating, Membrane Potentials, Muscarinic Agonists, Myocytes, Smooth Muscle, Receptors, G-Protein-Coupled, Receptors, Muscarinic, TRPC Cation Channels, Science & Technology, Life Sciences & Biomedicine, Physiology, PHYSIOLOGY, Markov chain, channel kinetics, G-protein, carbachol, smooth muscle, SMOOTH-MUSCLE-CELLS, GUINEA-PIG ILEUM, INDUCED INWARD CURRENT, BETA-GAMMA-SUBUNITS, ION CHANNELS, END-PLATE, INTERNAL CALCIUM, PHOSPHOLIPASE-C, K+ CHANNEL, CURRENTS, Markov chain, channel kinetics, G-protein, carbachol, smooth muscle, Physiology, 0606 Physiology, 1116 Medical Physiology
Journal or Publication Title: JOURNAL OF GENERAL PHYSIOLOGY
ISSN: 0022-1295
Related URLs:
Dates:
DateEvent
26 April 2004Published
Web of Science ID: WOS:000221372400009
URI: https://openaccess.sgul.ac.uk/id/eprint/107180
Publisher's version: https://doi.org/10.1085/jgp.200309002

Actions (login required)

Edit Item Edit Item