Unique Kir2.x Properties Determine Regional and Species Differences in the Cardiac Inward Rectifier K + Current

Abstract

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 (I≈0 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.