Journal
BIOPHYSICAL JOURNAL
Volume 101, Issue 6, Pages 1354-1363Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2011.08.015
Keywords
-
Categories
Funding
- National Institutes of Health/National Heart, Lung, and Blood Institute [HL079275, HL101190]
- Irma T. Hirschl Career Scientist Award
Ask authors/readers for more resources
Potassium currents generated by voltage-gated potassium (Kv) channels comprising alpha-subunits from the Kv1, 2, and 3 subfamilies facilitate high-frequency firing of mammalian neurons. Within these subfamilies, only three alpha-subunits (Kv1.4, Kv3.3, and Kv3.4) generate currents that decay rapidly in the open state because an N-terminal ball domain blocks the channel pore after activation-a process termed N-type inactivation. Despite its importance to shaping cellular excitability, little is known of the processes regulating surface expression of N-type alpha-subunits, versus their slowly inactivating (delayed rectifier) counterparts. Here we found that currents generated by homomeric Kv1.4, Kv3.3, and Kv3.4 channels are all strongly suppressed by the single transmembrane domain ancillary (beta) subunits KCNE1 and KCNE2. A combination of electrophysiological, biochemical, and immunofluorescence analyses revealed this suppression is due to KCNE1 and KCNE2 retaining Kv1.4 and Kv3.4 intracellularly, early in the secretory pathway. The retention is specific, requires alpha-beta coassembly, and does not involve the dynamin-dependent endocytosis pathway. However, the small fraction of Kv3.4 that escapes KCNE-dependent retention is regulated by dynamin-dependent endocytosis. The findings illustrate two contrasting mechanisms controlling surface expression of N-type Kv alpha-subunits and therefore, potentially, cellular excitability and refractory periods.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available