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 (IF) 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 If 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 mu M. In conclusion, I-f is significantly overexpressed in LVM from PMI rat hearts. In these cells, If 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. (c) 2006 Elsevier Ltd. All rights reserved.

Functional remodeling in post-myocardial infarcted rats: focus on beta-adrenoceptor subtypes / L. SARTIANI; P. DEPAOLI; F. STILLITANO; F. AIMOND; G. VASSORT; A. MUGELLI; E. CERBAI. - In: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. - ISSN 0022-2828. - STAMPA. - 40:(2006), pp. 258-266. [10.1016/j.yjmcc.2005.11.011]

Functional remodeling in post-myocardial infarcted rats: focus on beta-adrenoceptor subtypes.

SARTIANI, LAURA;STILLITANO, FRANCESCA;MUGELLI, ALESSANDRO;CERBAI, ELISABETTA
2006

Abstract

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 (IF) 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 If 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 mu M. In conclusion, I-f is significantly overexpressed in LVM from PMI rat hearts. In these cells, If 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. (c) 2006 Elsevier Ltd. All rights reserved.
2006
40
258
266
L. SARTIANI; P. DEPAOLI; F. STILLITANO; F. AIMOND; G. VASSORT; A. MUGELLI; E. CERBAI
File in questo prodotto:
File Dimensione Formato  
Sartiani_JMCC_2006.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 386.87 kB
Formato Adobe PDF
386.87 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/309970
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 24
social impact