ROLE OF THE KV4.3 K- A MOLECULAR CORRELATE FOR THE TRANSIENT OUTWARD CURRENT( CHANNEL IN VENTRICULAR MUSCLE )

The expression of 15 different K+ channels in canine heart was examine d, and a new K+ channel gene (Kv4.3), which encodes a rapidly inactiva ting K+ current, is described. The Kv4.3 channel was found to have bio physical and pharmacological properties similar to the native canine t ransient outward current (I-to). The Kv4.3 gene is also expressed in h uman and rat heart. It is concluded that the Kv4.3 channel underlies t he bulk of the I-to in canine ventricular myocytes, and probably in hu man myocytes. Both the Kv4.3 and Kv4.2 channels are likely to contribu te to the I-to in rat heart, and differential expression of these two channels can account for observed differences in the kinetic propertie s of the I-to in different regions of rat ventricle. There are signifi cant differences in the pattern of K+ channel expression in canine hea rt,compared with rat heart, and these differences may be an adaptation to the different requirements for cardiac function in mammals of mark edly different sizes. It is possible that the much longer ventricular action potential duration observed in canine heart compared with rat h eart is due, in part, to the lower levels of Kv1.2, Kv2.1, and Kv4.2 g ene expression in canine heart.