TY - JOUR
T1 - Functional remodeling in post-myocardial infarcted rats
T2 - Focus on beta-adrenoceptor subtypes
AU - Sartiani, Laura
AU - De Paoli, Petra
AU - Stillitano, Francesca
AU - Aimond, Frank
AU - Vassort, Guy
AU - Mugelli, Alessandro
AU - Cerbai, Elisabetta
PY - 2006/2
Y1 - 2006/2
N2 - 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 β1-, β2- and β3-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 If were similar. β1AR stimulation with noradrenaline caused a rightward shift of VH 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 β1AR in PMI cells (86.6% vs. SHAM cells), but did not affect β1AR response in SHAM cells. β2AR response was significantly and equally increased by PTX-pretreatment (by 94% in SHAM and 87% in PMI cells). Conversely, β3AR 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). β3AR response was blunted by PTX-pretreatment, by incubation with NG-monomethyl-l- arginine acetate or by the selective β3AR antagonist SR 59230A 1 μM. In conclusion, If is significantly overexpressed in LVM from PMI rat hearts. In these cells, If modulation by β1AR is significantly depressed while β3AR modulation is markedly enhanced, probably reflecting the increased activity of PTX-sensitive G i proteins in PMI cells.
AB - 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 β1-, β2- and β3-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 If were similar. β1AR stimulation with noradrenaline caused a rightward shift of VH 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 β1AR in PMI cells (86.6% vs. SHAM cells), but did not affect β1AR response in SHAM cells. β2AR response was significantly and equally increased by PTX-pretreatment (by 94% in SHAM and 87% in PMI cells). Conversely, β3AR 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). β3AR response was blunted by PTX-pretreatment, by incubation with NG-monomethyl-l- arginine acetate or by the selective β3AR antagonist SR 59230A 1 μM. In conclusion, If is significantly overexpressed in LVM from PMI rat hearts. In these cells, If modulation by β1AR is significantly depressed while β3AR modulation is markedly enhanced, probably reflecting the increased activity of PTX-sensitive G i proteins in PMI cells.
KW - β-Adrenenergic receptors
KW - Heart failure
KW - Hyperpolarization-activated current
KW - Infarction
KW - Inhibitory G proteins
UR - http://www.scopus.com/inward/record.url?scp=31444437224&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2005.11.011
DO - 10.1016/j.yjmcc.2005.11.011
M3 - Article
C2 - 16427077
AN - SCOPUS:31444437224
SN - 0022-2828
VL - 40
SP - 258
EP - 266
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 2
ER -