Modulation of calcium-activated potassium channels from rat brain by protein kinase A and phosphatase 2A

• Published in: The Journal of neuroscience Vol. 11; no. 6; pp. 1627 - 1635
• Main Authors: Reinhart, PH, Chung, S, Martin, BL, Brautigan, DL, Levitan, IB
• Format: Journal Article
• Language: English
• Published: Washington, DC Soc Neuroscience 01-06-1991; Society for Neuroscience
• Subjects: Animals; Biological and medical sciences; brain; Brain - physiology; Calcium - pharmacology; Cell Membrane - physiology; Central nervous system; Electric Conductivity - drug effects; Electrophysiology; Fundamental and applied biological sciences. Psychology; Ion Channel Gating - drug effects; Kinetics; Lipid Bilayers; Membrane Fusion; Membrane Potentials - drug effects; phosphoprotein phosphatase; Phosphoprotein Phosphatases - pharmacology; potassium; Potassium Channels - drug effects; Potassium Channels - physiology; protein kinase A; Protein Kinases - pharmacology; Protein Phosphatase 1; Protein Phosphatase 2; Rats; synaptic vesicles; Time Factors; Vertebrates: nervous system and sense organs; Brain; Phosphorylation; Calcium; Rat; Enzyme; Rodentia; Central nervous system; Electrophysiology; Ionic channel; Ionic current; Phosphatase; Vertebrata; Mammalia; Protein kinase; Potassium
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.11-06-01627.1991

By incorporating plasma membrane vesicles into planar lipid bilayers, we previously characterized a family of four types of Ca(2+)-activated K+ channels from rat brain (Reinhart et al., 1989). Two of these are "large-conductance" or "maxi"-K+ channels, which differ in their gating kinetics and toxin sensitivity and are henceforth referred to as "type 1" and "type 2" channels. Here we show that the gating of these two channel types can be modulated by phosphorylation and dephosphorylation. The effects of cAMP-dependent protein kinase catalytic subunit (PK-A) on type 1 maxi-K+ channels are complex in that, while half of these channels are upregulated by the kinase, about one out of seven channels is downregulated. Thus, there may be several distinct channels within the type 1 category. Type 2 maxi-K+ channels are consistently downregulated by PK-A. The effects of PK-A on both channel types are reversed by the catalytic subunit of protein phosphatase 2A (PP-2A), but not by protein phosphatase 1 (PP-1). Furthermore, some of the type 1 maxi-K+ channels can be modulated by PP-2A, even without any prior PK-A treatment, indicating they are in a phosphorylated state when they are incorporated into the bilayer. The results demonstrate that (1) type 1 and type 2 maxi-K+ channels are substrates for PK-A; (2) phosphorylation can shift the open probability of channels in either direction, by a mechanism involving multiple phosphorylation sites; (3) phosphorylation alters the Ca2+/voltage sensitivity of these channels; and (4) dephosphorylation of type 1 and type 2 channels is catalyzed by specific phosphatases.