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Suarez-Delgado, Esteban; Rangel-Sandin, Teriws G; Ishida, Itzel G; Rangel-Yescas, Gisela E; Rosenbaum, Tamara; Islas, Leon D (2020)

K(V)1.2 CHANNELS INACTIVATE THROUGH A MECHANISM SIMILAR TO C-TYPE INACTIVATION

J. Gen. Physiol. 152(6):
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Slow inactivation has been described in multiple voltage-gated K+ channels and in great detail in the Drosophila Shaker channel. Structural studies have begun to facilitate a better understanding of the atomic details of this and other gating mechanisms. To date, the only voltage-gated potassium channels whose structure has been solved are KvAP (x-ray diffraction), the KV1.2-KV2.1 "paddle" chimera (x-ray diffraction and cryo-EM), KV1.2 (x-ray diffraction), and ether-à-go-go (cryo-EM); however, the structural details and mechanisms of slow inactivation in these channels are unknown or poorly characterized. Here, we present a detailed study of slow inactivation in the rat KV1.2 channel and show that it has some properties consistent with the C-type inactivation described in Shaker. We also study the effects of some mutations that are known to modulate C-type inactivation in Shaker and show that qualitative and quantitative differences exist in their functional effects, possibly underscoring subtle but important structural differences between the C-inactivated states in Shaker and KV1.2.