BETA-ADRENERGIC AND MUSCARINIC RECEPTOR MESSENGER-RNA ACCUMULATION INTHE SINOATRIAL NODE AREA OF ADULT AND SENESCENT RAT HEARTS

The sinoatrial (SA) node is the cardiac pacemaker and changes in its a drenergic-muscarinic phenotype have been postulated as a determinant o f age-associated modifications in heart rate variability. To address t his question, right atria were microdissected, the SA node area was id entified by acetylcholinesterase staining, and, using a RT-PCR method, the accumulation of mRNA molecules encoding beta(1)- and beta(2)-adre nergic (beta(1)- and beta(2)-AR) and muscarinic (M-2-R) receptor was q uantified to define the proportion between beta-AR and M-2-R mRNAs wit hin the sinoatrial area of adult (3 months) and senescent (24 months) individual rat hearts. In adult hearts, the highest M-2-R/beta-AR mRNA ratio was observed within the sinoatrial area compared with adjacent atrial myocardium, while in the senescent hearts, no difference was ob served between sinoatrial and adjacent areas. This change was specific of the sinoatrial area since adult and senescent whole atrial or vent ricular myocardium did not differ in their M-2-R/beta-AR mRNA ratio, a nd was associated with a fragmentation of acetylcholinesterase stainin g of the senescent SA node. Quantitative changes in the expression of genes encoding proteins involved in heart rate regulation specifically affect the sinoatrial area of the senescent heart. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.