β-Adrenergic stimulation does not activate Na⁺/Ca²⁺ exchange current in guinea pig, mouse, and rat ventricular myocytes

This is the authors' abstract. We don't add key points for this paper.

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.

Challenges prior reports of beta-adrenergic NCX augmentation in rodents; leaves open translation to human myocytes.