A novel subunit for Shal K⁺ channels radically alters activation and inactivation

Shal (Kv4) potassium channel genes encode classical subthreshold A- currents, and their regulation may be a key factor in determining neuronal firing frequency. The inactivation rate of Shal channels is increased by a presently unidentified class of proteins in both Drosophila and mammals. We have cloned a novel Shal channel subunit (jShalγ1) from the jellyfish Polyorchis penicillatus that alters Shal currents from both invertebrates and vertebrates. When co-expressed with the conserved jellyfish Shal homolog jShal1, jShalγ1 dramatically changes both the rate of inactivation and voltage range of activation and steady-state inactivation. jShalγ1 provides fast inactivation by a classic N-type mechanism, which is independent of its effects on voltage dependence. jShalγ1 forms functional channels only as a heteromultimer, and jShalγ1 + jShal1 heteromultimers are functional only in a 2:2 subunit stoichiometry.