Association of the Kvl family of K~+ channels and their functional blueprint in the properties of auditory neurons as revealed by genetic and functional analyses

摘要

Developmental plasticity in spiral ganglion neurons (SGNs) ensues from profound alterations in the functional properties of the developing hair cell (HC). For example, prehearing HCs are spontaneously active. However, at the post-hearing stage, HC membrane properties transition to graded receptor potentials. The dendrotoxin (DTX)-sensitive Kvl channel subunits (Kv1.1, 1.2, and 1.6) shape the firing properties and membrane potential of SGNs, and the expression of the channel undergoes developmental changes. Because of the stochastic nature of Kv subunit heteromultimerization, it has been difficult to determine physiologically relevant subunit-specific interactions and their functions in the underlying mechanisms of Kvl channel plasticity in SGNs. Using Kcna2 null mutant mice, we demonstrate a surprising paradox in changes in the membrane properties of SGNs. The resting membrane potential of Kcna2~/~ SGNs was significantly hyperpolarized compared with that of age-matched wild-type (WT) SGNs. Analyses of outward currents in the mutant SGNs suggest an apparent approximately twofold increase in outward K~+ currents. We show that in vivo and in vitro heteromultimerization of Kv1.2 and Kvl.4 alpha-subunits underlies the striking and unexpected alterations in the properties of SGNs. The results suggest that heteromeric interactions of Kv1..2 and Kv1.4 dominate the defining features of Kvl channels in SGNs.