I-K OF RABBIT VENTRICLE IS COMPOSED OF 2 CURRENTS - EVIDENCE FOR I-KS

The delayed rectifier K+ current (I-K) in rabbit heart has long been t hought to consist of only a single, rapidly activating, dofetilide-sen sitive current, I-Kr. However, we find that I-K Of rabbit ventricular myocytes actually consists of both rapid and slow components, I-Kr and I-Ks, respectively, that can be isolated pharmacologically. Thus, aft er complete blockade of I-Kr with dofetilide, the remaining current, I -Ks, is homogeneous as judged by an envelope of tails test. I-Ks activ ates and deactivates slowly, continues to activate during sustained de polarizations, has a half-activation potential of 7.0 +/- 0.8 mV and s lope factor of 11.0 +/- 0.7 mV, reverses at -77.2 +/- 1.3 mV (extracel lular K+ concentration = 4 mM), is increased by removing extracellular K+, and is enhanced by isoproterenol and blocked by azimilide. Northe rn analysis demonstrates that the minK (I-sK) gene, which encodes a su bunit of the channel that underlies the I-Ks current, is expressed in rabbit heart. Expression of the rabbit protein in Xenopus oocytes elic its a slowly activating, voltage-dependent current, I-sK, similar to t hose expressed previously from mouse, rat, guinea pig, and human genes . The results demonstrate that I-Ks is present in rabbit ventricle and therefore contributes to cardiac repolarization in this species.