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¹ Institute of Physiology, Ruhr-University Bochum, D-44780 Bochum, Germany

Apart from gating by interaction with β subunits from heterotrimeric G proteins upon stimulation of appropriate receptors, Kir.3 channels have been shown to be gated by intracellular Na⁺. However, no information is available on how Na⁺-dependent gating affects endogenous Kir3.1/Kir3.4 channels in mammalian atrial myocytes. We therefore studied how loading of adult atrial myocytes from rat hearts via the patch pipette filling solution with different concentrations of Na⁺ ([Na⁺]_pip) affects Kir3 current. Surprisingly, in a range between 0 and 60 mM, Na⁺ neither had an effect on basal inward-rectifier current nor on the current activated by acetylcholine. Overexpression of Kir3.4 in adult atrial myocytes forced by adenoviral gene transfer results in formation of functional homomeric channels that interact with β subunits upon activation of endogenous muscarinic receptors. These channels are activated at [Na⁺]_pip 15 mM, resulting in a receptor-independent basal inward rectifier current (I_bir). I_bir was neither affected by pertussis toxin nor by GDP-β-S, suggesting G-protein-independent activation. PIP₂ depletion via endogenous PLC-coupled ₁ adrenergic receptors causes inhibition of endogenous Kir3.1/3.4 channel currents by about 75%. In contrast, inhibition of Na⁺-activated I_bir amounts to < 20%. The effect of the Kir3 channel blocker tertiapin-Q can be described using an IC₅₀ of 12 nM (endogenous I_K(ACh)) and 0.61 nM (I_bir). These data clearly identify I_bir as a homotetrameric Kir3.4 channel current with novel properties of regulation and pharmacology. I_bir shares some properties with a basal current recently described in atrial myocytes from an animal model of atrial fibrillation (AF) and AF patients.

(Received 17 July 2007; accepted after revision 18 September 2007; first published online 20 September 2007)
Corresponding author L. Pott: Institute of Physiology, Ruhr-University Bochum, D 44780 Bochum, Germany. Email: lutz.pott{at}rub.de

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