Article

Meera, P., Wallner, M., Song, M. & Toro, L. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc. Natl Acad. Sci. USA 94, 14066−14071

Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/1998; 94(25):14066-71. DOI: 10.1073/pnas.94.25.14066
Source: PubMed

ABSTRACT Large conductance voltage- and Ca2+-dependent K+ (MaxiK) channels show sequence similarities to voltage-gated ion channels. They have a homologous S1-S6 region, but are unique at the N and C termini. At the C terminus, MaxiK channels have four additional hydrophobic regions (S7-S10) of unknown topology. At the N terminus, we have recently proposed a new model where MaxiK channels have an additional transmembrane region (S0) that confers beta subunit regulation. Using transient expression of epitope tagged MaxiK channels, in vitro translation, functional, and "in vivo" reconstitution assays, we now show that MaxiK channels have seven transmembrane segments (S0-S6) at the N terminus and a S1-S6 region that folds in a similar way as in voltage-gated ion channels. Further, our results indicate that hydrophobic segments S9-S10 in the C terminus are cytoplasmic and unequivocally demonstrate that S0 forms an additional transmembrane segment leading to an exoplasmic N terminus.

Download full-text

Full-text

Available from: Martin Wallner, Aug 12, 2015
0 Followers
 · 
79 Views
  • Source
    • "The BK Ca channel is formed by homo-tetramers of αsubunits ; each subunit comprises seven conserved transmembrane domains (S0 through S6), an extracellular N terminus, and a large C-terminal domain (Wallner et al., 1996; Meera et al., 1997). The C-terminal domain encompasses four hydrophobic segments (S7–S10), two predicted regulators of K + conductance domains (RCK1 and RCK2), and a Ca 2+ sensor domain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The large-conductance voltage- and Ca(2+)-activated K(+) channel (BKCa) is an important regulator of membrane excitability in a wide variety of cells and tissues. In myometrial smooth muscle, activation of BKCa plays essential roles in buffering contractility to maintain uterine quiescence during pregnancy and in the transition to a more contractile state at the onset of labor. Multiple mechanisms of modulation have been described to alter BKCa channel activity, expression, and cellular localization. In the myometrium, BKCa is regulated by alternative splicing, protein targeting to the plasma membrane, compartmentation in membrane microdomains, and posttranslational modifications. In addition, interaction with auxiliary proteins (i.e., β1- and β2-subunits), association with G-protein coupled receptor signaling pathways, such as those activated by adrenergic and oxytocin receptors, and hormonal regulation provide further mechanisms of variable modulation of BKCa channel function in myometrial smooth muscle. Here, we provide an overview of these mechanisms of BKCa channel modulation and provide a context for them in relation to myometrial function.
    Frontiers in Physiology 07/2014; 5:289. DOI:10.3389/fphys.2014.00289 · 3.50 Impact Factor
  • Source
    • "Each BK channel α-subunit consists of a total of seven transmembrane segments with a unique S0 segment that precedes the usually six transmembrane segments (S1-S6). The total of seven segments (S0-S6) renders the N-terminus (amino terminal) at the extracellular side of the membrane (Meera et al., 1997). Multiple splice variants of the αsubunit have been identified resulting in a great variety of channel properties in various cell types (Fodor & Aldrich, 2009). "
  • Source
    • "Ca 2+ ions are shown as green spheres. a functionally important interaction with the β1 subunit (Wallner et al., 1996; Meera et al., 1997; Morrow et al., 2006; Liu et al., 2008). The S0 segment also forms an integral part of the BK channel voltage-sensor domain (Koval et al., 2007; Pantazis et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Large-conductance Ca(2+)-activated K(+) channels (BK channels) constitute an key physiological link between cellular Ca(2+) signaling and electrical signaling at the plasma membrane. Thus these channels are critical to the control of action potential firing and neurotransmitter release in several types of neurons, as well as the dynamic control of smooth muscle tone in resistance arteries, airway, and bladder. Recent advances in our understanding of K(+) channel structure and function have led to new insight toward the molecular mechanisms of opening and closing (gating) of these channels. Here we will focus on mechanisms of BK channel gating by Ca(2+), transmembrane voltage, and auxiliary subunit proteins.
    Protein & Cell 09/2012; 3(12). DOI:10.1007/s13238-012-2076-8 · 2.85 Impact Factor
Show more

Similar Publications