Beta-adrenergic stimulation does not activate Na+/Ca2+ exchange current in guinea pig, mouse, and rat ventricular myocytes.
The effect of beta-adrenergic stimulation on cardiac Na(+)/Ca(2+) exchange has been controversial. To clarify the effect, we measured Na(+)/Ca(2+) exchange current (I(NCX)) in voltage-clamped guinea pig, mouse, and rat ventricular cells. When I(NCX) was defined as a 5 mM Ni(2+)-sensitive current in guinea pig ventricular myocytes, 1 microM isoproterenol apparently augmented I(NCX) by approximately 32%. However, this increase was probably due to contamination of the cAMP-dependent Cl(-) current (CFTR-Cl(-) current, I(CFTR-Cl)), because Ni(2+) inhibited the activation of I(CFTR-Cl) by 1 microM isoproterenol with a half-maximum concentration of 0.5 mM under conditions where I(NCX) was suppressed. Five or ten millimolar Ni(2+) did not inhibit I(CFTR-Cl) activated by 10 microM forskolin, an activator of adenylate cyclase, suggesting that Ni(2+) acted upstream of adenylate cyclase in the beta-adrenergic signaling pathway. Furthermore, in a low-extracellular Cl(-) bath solution, 1 microM isoproterenol did not significantly alter the amplitude of Ni(2+)-sensitive I(NCX) at +50 mV, which is close to the reversal potential of I(CFTR-Cl). No change in I(NCX) amplitude was induced by 10 microM forskolin. When I(NCX) was activated by extracellular Ca(2+), it was not significantly affected by 1 microM isoproterenol in guinea pig, mouse, or rat ventricular cells. We concluded that beta-adrenergic stimulation does not have significant effects on I(NCX) in guinea pig, mouse, or rat ventricular myocytes.
Lin
Xue
X
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan.
Jo
Hikari
H
Sakakibara
Yutaka
Y
Tambara
Keiichi
K
Kim
Bongju
B
Komeda
Masashi
M
Matsuoka
Satoshi
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology*; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; D005576:Colforsin; D009532:Nickel; D012964:Sodium; D007545:Isoproterenol; D002118:Calcium