ISSN:
1432-2013
Keywords:
Atrial myocytes
;
Muscarinic
;
Desensitization
;
Electrophysiology
;
Potassium channel
;
Calcium channel
;
G protein
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The time course of muscarinic effects on K and Ca currents was investigated at 22–24° C in guinea-pig atrial myocytes, using the whole-cell voltage clamp. At a holding potential of -40 or -50 mV, short exposures to 100 μM acetylcholine (ACh) or carbachol (CCh) reproducibly induced outward K currents (I K,ACh). During long exposures to these agonists, I K,ACh faded with time. In cells not dialysed with guanosine triphosphate (GTP), I K,ACh could dissipate completely following 15–20 min of agonist exposure. After agonist washout, lost sensitivity was not recovered. In cells dialysed with GTP (0.2–1 mM), I K,ACh still faded but normal sensitivity to agonists was restored with washout. Fade of I K,ACh was not prevented by intracellular heparin or dextran, excluding the involvement of either β-adrenergic or muscarinic receptor kinase. I K,ACh induced by bethanechol or adenosine also faded, and subsequent CCh application after washout revealed a diminished response. Intracellular guanosine-5′-o-(3-thiotriphosphate I K,ACh induced I K,ACh which faded, and subsequent exposure to CCh was without effect. Equally, after full desensitization with CCh, I K,ACh failed to induced I K,ACh. The Ca current (I Ca) was activated by voltage steps to 0 mV and increased with 1–3 μM isoproterenol. This increase could be reversed by CCh, even when I K,ACh had completely faded. Prolonged muscarinic agonist exposure sometimes also caused fade of the effect on I Ca, which always occurred after loss of I K,ACh. The results show that desensitization is heterologous and may involve the guanine nucleotide-binding (G) protein. The differential desensitization to the effects on I K,ACh and I Ca suggests the involvement of two different signalling pathways in the muscarinic control of K and Ca channels.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00374576
Permalink
