β-Adrenoceptor/PKA-stimulation, Na(+)–Ca(2+) exchange and PKA-activated Cl(−) currents in rabbit cardiomyocytes: A conundrum

Investigations into the functional modulation of the cardiac Na(+)–Ca(2+) exchanger (NCX) by acute β-adrenoceptor/PKA stimulation have produced conflicting results. Here, we investigated (i) whether or not β-adrenoceptor activation/PKA stimulation activates current in rabbit cardiac myocytes under NCX-‘selective’ conditions and (ii) if so, whether a PKA-activated Cl(−)-current may contribute to the apparent modulation of NCX current (I(NCX)). Whole-cell voltage-clamp experiments were conducted at 37 °C on rabbit ventricular and atrial myocytes. The β-adrenoceptor-activated currents both in NCX-‘selective’ and Cl(−)-selective recording conditions were found to be sensitive to 10 mM Ni(2+). In contrast, the PKA-activated Cl(−) current was not sensitive to Ni(2+), when it was activated downstream to the β-adrenoceptors using 10 μM forskolin (an adenylyl cyclase activator). When 10 μM forskolin was applied under NCX-selective recording conditions, the Ni(2+)-sensitive current did not differ between control and forskolin. These findings suggest that in rabbit myocytes: (a) a PKA-activated Cl(−) current contributes to the Ni(2+)-sensitive current activated via β-adrenoceptor stimulation under recording conditions previously considered selective for I(NCX); (b) downstream activation of PKA does not augment Ni(2+)-sensitive I(NCX), when this is measured under conditions where the Ni(2+)-sensitive PKA-activated Cl(−) current is not present.