Alpha 1-adrenoceptor stimulation increases intracellular pH and Ca2+ in cardiomyocytes through Na+/H+ and Na+/Ca2+ exchange.
The effects of alpha 1-adrenergic stimulation on intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were investigated in isolated rat cardiomyocytes with fluorescence dyes, BCECF and fura-2, respectively. In the presence of 5 or 25 mM HCO3- norepinephrine (NE) increased pHi in a dose-dependent manner. Intracellular alkalinization was inhibited by prazosin and phentolamine but not by yohimbine. NE-induced alkalinization was inhibited in the presence of a Na+/H+ exchange inhibitor (5-(N,N-hexamethylene) amiloride (HMA)), a C kinase inhibitor (H-7) or a calmodulin inhibitor (W-7), or in the absence of extracellular Na+. NE also increased [Ca2+]i following the pHi increase, which was abolished in the absence of extracellular Na+ or Ca2+. This Ca2+ influx was inhibited by HMA but not by diltiazem (10(-5) M). Thus, we conclude that alpha 1-adrenergic stimulation enhances Na+/H+ exchange by activation of C kinase, thereby allowing intracellular alkalinization, and that subsequent activation of Na+/Ca2+ exchange increases Ca2+ influx.
Iwakura
K
K
First Department of Medicine, Osaka University School of Medicine, Japan.
Hori
M
M
Watanabe
Y
Y
Kitabatake
A
A
Cragoe
E J
EJ
Yoshida
H
H
Kamada
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D005456:Fluorescent Dyes; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C057360:5-(N,N-hexamethylene)amiloride; D015016:Yohimbine; D000584:Amiloride; D006859:Hydrogen; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D011433:Propranolol; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine