Changes in the inactivation of rat Kv1.4 K+ channels induced by varying the number of inactivation particles

N-type inactivation of rat Kv1,4 channels with one, two, or four inactivati on balls was investigated using homogeneous populations of channels express ed in Xenopus oocytes, Tandem dimeric and tetrameric constructs of Kv1.4 we re made, Channels encoded by tandem cDNAs Kv1.4-Rv1.4 Delta 1-145 and Kv1.4 -[Kv1.4 Delta 1-145](3) have two or only one tethered inactivation ball, re spectively, whereas Kv1,4 itself encodes channels having four inactivation balls. The time constants for inactivation of macroscopic currents were inc reased significantly as the number of inactivation balls was decreased, whe reas the time constants for recovery from inactivation were not modified. T he ratios of the rate constants of inactivation (k(inact)) of Kv1.4-Kv1.4 D elta 1-145 and Kv1.4-[Kv1.4 Delta-145](3) channels to that of the Kv1,4 cha nnel were 0.65 and 0.4, respectively, whereas the ratios of the rate consta nt of recovery (k(rec)) of these channels to that of Kv1,4 were almost unit y. The rate constants k(inact) for channels having two and four inactivatio n balls are smaller than those that would be expected if inactivation balls on each channel are independent, suggesting some interaction occurs betwee n inactivation balls. Furthermore, noninactivating current became apparent as the number of inactivation balls on a channel was decreased.