Article

Conditional and Unconditional Inhibition of Calcium-activated Potassium Channels by Reversible Protein Phosphorylation

Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2000; 275(6):3749-54. DOI: 10.1074/jbc.275.6.3749
Source: PubMed

ABSTRACT

Large conductance, calcium-activated potassium channels (BKCa or maxi-K) are important determinants of membrane excitability in many cell types. We used patch clamp techniques to study
the biochemical regulation of native BKCa channel proteins by endogenous Ser/Thr-directed protein kinases and phosphatases in cell-free membrane patches from rat pituitary
tumor cells (GH4C1). When protein kinase activity was blocked by removing ATP, endogenous protein phosphatases slowly increased BKCa channel activity approximately 3-fold. Dephosphorylated channels could be activated fully by physiological increases in cytoplasmic
calcium or membrane depolarization. In contrast, endogenous protein kinases inhibited BKCa channel activity at two functionally distinct sites. A closely associated, cAMP-dependent protein kinase rapidly reduced
channel activity in a conditional manner that could be overcome completely by increasing cytoplasmic free calcium 3-fold or
20 mV further depolarization. Phosphorylation at a pharmacologically distinct site inhibited channel activity unconditionally
by reducing availability to approximately half that of maximum at all physiological calcium and voltages. Conditional versus unconditional inhibition of BKCa channel activity through different protein kinases provides cells with a powerful computational mechanism for regulating
membrane excitability.

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    • "PKA has been reported to activate, inhibit or have no effect on BK channels as reviewed by Schubert and Nelson (2001). These different actions appear to depend on alternative BK splicing or could reflect variants in α and β subunit composition of the channel complexes (Hall and Armstrong, 2000; Tian et al., 2001, 2004). At PKA primed channels H 2 S only had a high significant effect on BK channel Po from GH3 cells but had no effect on GH4 and GH4 STREX cells. "

    Full-text · Article · Jan 2014
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    • "Patch clamp recordings revealed that STREX causes BK channels to activate at more negative potentials and enhances activation and decreases deactivation which leads to increased repetitive firing of action potentials. STREX can be artificially induced by growing cells in phenol red which causes a significant increase in channel sensitivity to inhibition by oxidation but also to Ca 2+ (Hall & Armstrong 2000). Coassembly of STREX/β1-subunits, however, could only be stimulated with a truncated Nterminus variation present which has physiological impact of channel regulation by Ca 2+ , oxidation, and phosphorylation. "

    Full-text · Dataset · Nov 2013
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    • "Patch clamp recordings revealed that STREX causes BK channels to activate at more negative potentials and enhances activation and decreases deactivation which leads to increased repetitive firing of action potentials. STREX can be artificially induced by growing cells in phenol red which causes a significant increase in channel sensitivity to inhibition by oxidation but also to Ca 2+ (Hall & Armstrong 2000). Coassembly of STREX/β1-subunits, however, could only be stimulated with a truncated Nterminus variation present which has physiological impact of channel regulation by Ca 2+ , oxidation, and phosphorylation. "
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