LOW-MOLECULAR-WEIGHT POLY(A)-RNA SPECIES ENCODE FACTORS THAT MODULATEGATING OF A NON-SHAKER A-TYPE K+ CHANNEL( MESSENGER)

Voltage-dependent K+ channels control repolarization of action potenti als and help establish fixing patterns in nerve cells. To determine th e nature and role of molecular components that modulate K+ channel fun ction in vivo, we coinjected Xenopus oocytes with cRNA encoding a clon ed subthreshold A-type K+ channel (mShal1, also referred to as mKv4.1) and a low molecular weight (LMW) fraction (2-4 kb) of poly(A)+ mRNA ( both from rodent brain). Coinjected oocytes exhibited a significant (f ourfold) increase in the surface expression of mShal1 K+ channels with no change in the open-channel conductance. Coexpression also modified the gating kinetics of mShal1 current in several respects. Macroscopi c inactivation of whole oocyte currents was fitted with the sum of two exponential components. Both fast and slow time constants of inactiva tion were accelerated at all membrane potentials in coinjected oocytes (tau(f) = 47.2 ms vs 56.5 ms at 0 mV and tau(s) = 157 ms vs 225 ms at 0 mV), and the corresponding ratios of amplitude terms were shifted t oward domination by the fast component (A(f)/A(s) = 2.71 vs 1.17 at 0 mV). Macroscopic activation was characterized in terms of the time-to- peak current, and it was found to be more rapid at all membrane potent ials in coinjected oocytes (9.9 ms vs 13.5 ms at 0 mV). Coexpression a lso leads to more rapid recovery from inactivation (approximately 2.4- fold faster at -100 mV). The coexpressed K+ currents in oocytes resemb le currents expressed in mouse fibroblasts (NIH3T3) transfected only w ith mShal1 cDNA. These results indicate that mammalian regulatory subu nits or enzymes encoded by LMW mRNA species, which are apparently miss ing or expressed at low levels in Xenopus oocytes, may modulate gating in some native subthreshold A-type K+ channels.