Regulation of Voltage-Dependent Channel Function

1988 ◽  
Author(s):  
Steven N. Treistman
Keyword(s):  
Channel Function ◽  
Voltage Dependent

scholarly journals LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells

2019 ◽  
Vol 116 (37) ◽  
pp. 18397-18403 ◽  
Author(s):  
Christopher J. Lingle ◽  
Pedro L. Martinez-Espinosa ◽  
Aizhen Yang-Hood ◽  
Luis E. Boero ◽  
Shelby Payne ◽  
...  
Keyword(s):  
Hair Cells ◽  
Glutamate Release ◽  
Nerve Fibers ◽  
Bk Channels ◽  
Bk Channel ◽  
Membrane Potentials ◽  
Macromolecular Complex ◽  
Inner Hair Cells ◽  
Channel Function ◽  
Voltage Dependent

The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca2+- and voltage-activated large conductance Ca2+-activated K+channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (−60 mV) even in the absence of intracellular Ca2+elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca2+channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat–containing (LRRC) regulatory γ subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs fromLrrc26knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs fromLrrc52KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK α subunits shifts BK current gating about −90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning.

Molecular Insights into Regulation of L-Type Ca Channel Function

Physiology ◽  
1991 ◽  
Vol 6 (6) ◽  
pp. 277-281 ◽  
Author(s):  
P Lory ◽  
G Varadi ◽  
A Schwartz
Keyword(s):  
Structure Function ◽  
Splice Variants ◽  
Ca Channel ◽  
Gene Products ◽  
Ca Channels ◽  
Channel Activity ◽  
Excitable Cells ◽  
Multiple Gene ◽  
Channel Function ◽  
Voltage Dependent

The diversity of voltage-dependent Ca channels is well documented. How excitable cells produce their specific Ca channel activity is being approached by structure-function studies. The implications of multiple gene products, splice variants, and subunit assembly in Ca channel function are updated in this review.

scholarly journals Voltage-Dependent Sodium Channel Function Is Regulated Through Membrane Mechanics

1999 ◽  
Vol 77 (4) ◽  
pp. 1945-1959 ◽  
Author(s):  
Anatoly Shcherbatko ◽  
Fumihito Ono ◽  
Gail Mandel ◽  
Paul Brehm
Keyword(s):  
Sodium Channel ◽  
Membrane Mechanics ◽  
Channel Function ◽  
Voltage Dependent

scholarly journals Thiazolidinedione insulin sensitizers alter lipid bilayer properties and voltage-dependent sodium channel function: implications for drug discovery

2011 ◽  
Vol 138 (2) ◽  
pp. 249-270 ◽  
Author(s):  
Radda Rusinova ◽  
Karl F. Herold ◽  
R. Lea Sanford ◽  
Denise V. Greathouse ◽  
Hugh C. Hemmings ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Gene Activation ◽  
Transport Processes ◽  
Titration Calorimetry ◽  
Peroxisome Proliferator ◽  
Inactivation Curve ◽  
Channel Function ◽  
Voltage Dependent ◽  
Target Effects

The thiazolidinediones (TZDs) are used in the treatment of diabetes mellitus type 2. Their canonical effects are mediated by activation of the peroxisome proliferator–activated receptor γ (PPARγ) transcription factor. In addition to effects mediated by gene activation, the TZDs cause acute, transcription-independent changes in various membrane transport processes, including glucose transport, and they alter the function of a diverse group of membrane proteins, including ion channels. The basis for these off-target effects is unknown, but the TZDs are hydrophobic/amphiphilic and adsorb to the bilayer–water interface, which will alter bilayer properties, meaning that the TZDs may alter membrane protein function by bilayer-mediated mechanisms. We therefore explored whether the TZDs alter lipid bilayer properties sufficiently to be sensed by bilayer-spanning proteins, using gramicidin A (gA) channels as probes. The TZDs altered bilayer elastic properties with potencies that did not correlate with their affinity for PPARγ. At concentrations where they altered gA channel function, they also altered the function of voltage-dependent sodium channels, producing a prepulse-dependent current inhibition and hyperpolarizing shift in the steady-state inactivation curve. The shifts in the inactivation curve produced by the TZDs and other amphiphiles can be superimposed by plotting them as a function of the changes in gA channel lifetimes. The TZDs’ partition coefficients into lipid bilayers were measured using isothermal titration calorimetry. The most potent bilayer modifier, troglitazone, alters bilayer properties at clinically relevant free concentrations; the least potent bilayer modifiers, pioglitazone and rosiglitazone, do not. Unlike other TZDs tested, ciglitazone behaves like a hydrophobic anion and alters the gA monomer–dimer equilibrium by more than one mechanism. Our results provide a possible mechanism for some off-target effects of an important group of drugs, and underscore the importance of exploring bilayer effects of candidate drugs early in drug development.

scholarly journals Structural motifs underlying voltage-dependent K+ channel function

1995 ◽  
Vol 48 (4) ◽  
pp. 918-922 ◽  
Author(s):  
Maurizio Taglialatela ◽  
Arthur M. Brown
Keyword(s):  
K Channel ◽  
Structural Motifs ◽  
Channel Function ◽  
Voltage Dependent

Structural Correlates of K+ Channel Function

Physiology ◽  
1994 ◽  
Vol 9 (4) ◽  
pp. 169-173 ◽  
Author(s):  
M Taglialatela ◽  
AM Brown
Keyword(s):  
Ion Channel ◽  
Ionic Currents ◽  
The Other ◽  
K Channel ◽  
K Channels ◽  
Functional Studies ◽  
Channel Function ◽  
Voltage Dependent ◽  
K Currents

More complementary DNAs have been cloned for Voltage-dependent K+ channels than any other voltage-dependent ion channel. Purely functional studies anticipated this result because K+ currents are far more diverse than voltage-dependent Na+, Ca2+, or Cl currents, the other types of voltage-dependent ionic currents commonly dealt with.

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