Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current

The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (I-K1). In addition to differences in current density, atrial and ventricular I-K1 have differences in outward current profiles and in extracellular potassium ([K+](o)) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular I-K1 in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than -30 mV (Iapproximate to0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, I-K1 rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, I-K1 did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1 +/- 0.1 pS in 15 cells, which corresponded with I-K1 in sheep atria (9.9 +/- 0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K+](o), whereas Kir2.3 currents did not increase. Correspondingly, guinea pig ( but not sheep) atrial I-K1 showed an increase in outward currents in 10 mmol/L [K+](o). Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward I-K1 currents rectified completely and increased in high [K+](o)-displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+](o) were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of I-K1 in the heart.