A new mode of regulation of N-type inactivation in a Caenorhabditis elegans voltage-gated potassium channel.
N-type inactivation in voltage-gated K+ (Kv) channels is a widespread means to modulate neuronal excitability and signaling. Here we have shown a novel mechanism of N-type inactivation in a Caenorhabditis elegans Kv channel. The N-terminal sequence of KVS-1 contains a domain of 22 amino acids that resembles the inactivation ball in A-type channels, which is preceded by a domain of eighteen amino acids. Wild type KVS-1 currents can be described as A-type; however, their kinetics are significantly (approximately 5-fold) slower. When the putative inactivation ball is deleted, the current becomes non-inactivating. Inactivation is restored in non-inactivating channels by diffusion of the missing inactivation domain in the cytoplasm. Deletion of the domain in front of the ball speeds inactivation kinetics approximately 5-fold. We conclude that KVS-1 is the first example of a novel type of Kv channel simultaneously possessing an N-inactivating ball preceded by an N inactivation regulatory domain (NIRD) that acts to slow down inactivation through steric mechanisms.
Cai
Shi-Qing
SQ
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854.
Sesti
Federico
F
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854. Electronic address: sestife@UMDNJ.EDU.
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; C522188:KVS-1 protein, C elegans; D024642:Potassium Channels, Voltage-Gated