In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 86, No. 6 ( 2000-03-31), p. 643-648
Abstract:
Abstract —In adult rat atrial myocytes, muscarinic acetylcholine (ACh)-sensitive K + current activated by a saturating concentration of adenosine ( I K(ACh),(Ado) ) via A 1 receptors (A 1 Rs) amounts to only 30% of the current activated by a saturating concentration of ACh ( I K(ACh),(ACh) ) via muscarinic M 2 receptors. The half-time of activation of I K(ACh),(Ado) on a rapid exposure to agonist was ≈4-fold longer than that of I K(ACh),(ACh) . Furthermore, I K(ACh),(Ado) never showed fast desensitization. To study the importance of receptor density for A 1 R- I K(ACh),(Ado) signaling, adult atrial myocytes in vitro were transfected with cDNA encoding for rat brain A 1 R and enhanced green fluorescent protein (EGFP) as a reporter. Whole-cell current was measured on days 3 and 4 after transfection. Time-matched cells transfected with only the EGFP vector served as controls. In ≈30% of EGFP-positive cells (group I), the density of I K(ACh),(Ado) was increased by 72%, and its half-time of activation was reduced. Density and kinetic properties of I K(ACh),(ACh) were not affected in this fraction. In ≈70% of transfection-positive myocytes (group II), the density of I K(ACh),(ACh) was significantly reduced, its activation was slowed, and the fast desensitizing component was lost. Adenosine-induced currents were larger in group II than in group I, their activation rate was further increased, and a fast desensitizing component developed. These data indicate that in native myocytes the amplitude and activation kinetics of I K(ACh),(Ado) are limited by the expression of A 1 R. Overexpression of A 1 R negatively interferes with signal transduction via the muscarinic M 2 receptor–linked pathway, which might reflect a competition of receptors with a common pool of G proteins. Negative interference of an overexpressed receptor with physiological regulation of a target protein by a different receptor should be considered in attempts to use receptor overexpression for gene therapy.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.86.6.643
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2000
detail.hit.zdb_id:
1467838-X
Permalink
