Stability of N-type inactivation and the coupling between N-type and C-type inactivation in the Aplysia Kv1 channel

• Published in: Pflügers Archiv 2024-10, Vol.476 (10), p.1493-1516
• Main Authors: Iwamuro, Tokunari, Itohara, Kazuki, Furukawa, Yasuo
• Format: Article
• Language: English
• Subjects: Animals; Aplysia; Aplysia - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Human Physiology; Insects; Ion Channel Gating - physiology; Ion Channels; Laboratory animals; Molecular Medicine; Neurosciences; Ovaries; Physiology; Plasmids; Potassium; Potassium channels (voltage-gated); Receptors; Receptors and Transporters; RNA polymerase; Shaker Superfamily of Potassium Channels - chemistry; Shaker Superfamily of Potassium Channels - genetics; Shaker Superfamily of Potassium Channels - metabolism; Xenopus laevis
• ISSN: 0031-6768; 1432-2013; 1432-2013
• DOI: 10.1007/s00424-024-02982-5

The voltage-dependent potassium channels (Kv channels) show several different types of inactivation. N-type inactivation is a fast inactivating mechanism, which is essentially an open pore blockade by the amino-terminal structure of the channel itself or the auxiliary subunit. There are several functionally discriminatable slow inactivation (C-type, P-type, U-type), the mechanism of which is supposed to include rearrangement of the pore region. In some Kv1 channels, the actual inactivation is brought about by coupling of N-type and C-type inactivation (N-C coupling). In the present study, we focused on the N-C coupling of the Aplysia Kv1 channel (AKv1). AKv1 shows a robust N-type inactivation, but its recovery is almost thoroughly from C-type inactivated state owing to the efficient N-C coupling. In the I8Q mutant of AKv1, we found that the inactivation as well as its recovery showed two kinetic components apparently correspond to N-type and C-type inactivation. Also, the cumulative inactivation which depends on N-type mechanism in AKv1 was hindered in I8Q, suggesting that N-type inactivation of I8Q is less stable. We also found that Zn 2 + specifically accelerates C-type inactivation of AKv1 and that H382 in the pore turret is involved in the Zn 2 + binding. Because the region around Ile 8 (I8) in AKv1 has been suggested to be involved in the pre-block binding of the amino-terminal structure, our results strengthen a hypothesis that the stability of the pre-block state is important for stable N-type inactivation as well as the N-C coupling in the Kv1 channel inactivation.