Functional remodeling in post-myocardial infarcted rats: focus on beta-adrenoceptor subtypes.
Cellular electrophysiological remodeling of the infarcted heart may lead to the deterioration of cardiac function and/or to arrhythmias. The present study was designed to characterize the functional expression of the hyperpolarization-activated current (I(f)) and its modulation by beta(1)-, beta(2)- and beta(3)-adrenoceptor (AR) subtypes, in patch-clamped ventricular myocytes isolated from the heart of post-myocardial infarcted (PMI) rats and sham-operated control (SHAM) rats. Maximum specific conductance of I(f) was significantly higher in left ventricular myocytes (LVM) from PMI rats compared to right ventricular myocytes from PMI rats as well as LVM and RVM from SHAM rats. All other basic properties of I(f) were similar. beta(1)AR stimulation with noradrenaline caused a rightward shift of V(H) in LVM from PMI rats which was significantly smaller (52.2%) than in LVM from SHAM rats. Incubation with pertussis toxin (PTX) largely restored the effect of beta(1)AR in PMI cells (86.6% vs. SHAM cells), but did not affect beta(1)AR response in SHAM cells. beta(2)AR response was significantly and equally increased by PTX-pretreatment (by 94% in SHAM and 87% in PMI cells). Conversely, beta(3)AR stimulation by the selective agonist SR 58611A caused a leftward shift of the activation curve which was significantly larger in PMI cells than in SHAM cells (P<0.01). beta(3)AR response was blunted by PTX-pretreatment, by incubation with N(G)-monomethyl-l-arginine acetate or by the selective beta(3)AR antagonist SR 59230A 1 microM. In conclusion, I(f) is significantly overexpressed in LVM from PMI rat hearts. In these cells, I(f) modulation by beta(1)AR is significantly depressed while beta(3)AR modulation is markedly enhanced, probably reflecting the increased activity of PTX-sensitive G(i) proteins in PMI cells.
Sartiani
Laura
L
Department of Preclinical and Clinical Pharmacology, Center of Molecular Medicine (CIMMBA), University of Florence, Viale G. Pieraccini 6, 50139 Firenze, Italy.
De Paoli
Petra
P
Stillitano
Francesca
F
Aimond
Frank
F
Vassort
Guy
G
Mugelli
Alessandro
A
Cerbai
Elisabetta
E
D000818:Animals; D002478:Cells, Cultured; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D019206:GTP-Binding Protein alpha Subunits, Gi-Go