scholarly journals How and why are calcium currents curtailed in the skeletal muscle voltage-gated calcium channels?

2017 ◽  
Vol 595 (5) ◽  
pp. 1451-1463 ◽  
Author(s):  
Bernhard E. Flucher ◽  
Petronel Tuluc
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Calcium Currents ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

Calcium- and Calmodulin-Dependent Inactivation of Calcium Channels in Inner Hair Cells of the Rat Cochlea

2008 ◽  
Vol 99 (5) ◽  
pp. 2183-2193 ◽  
Author(s):  
Lisa Grant ◽  
Paul Fuchs
Keyword(s):  
Calcium Channels ◽  
Hair Cells ◽  
Calcium Currents ◽  
Resting Potential ◽  
Resting Membrane Potential ◽  
Inner Hair Cells ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Dependent Inactivation ◽  
Calcium Buffering

Modulation of voltage-gated calcium channels was studied in inner hair cells (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti. Whole cell voltage clamp in the presence of potassium channel blockers showed inward calcium currents with millisecond activation and deactivation kinetics. When temperature was raised from 22 to 37°C, the calcium currents of immature IHCs [<12 days postnatal (P12)] increased threefold in amplitude, and developed more pronounced inactivation. This was determined to be calcium-dependent inactivation (CDI) on the basis of its reliance on external calcium (substitution with barium), sensitivity to internal calcium-buffering, and voltage dependence (reflecting the calcium driving force). After the onset of hearing at P12, IHC calcium current amplitude and the extent of inactivation were greatly reduced. Although smaller than in prehearing IHCs, CDI remained significant in the mature IHC near the resting membrane potential. CDI in mature IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo-hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of calcium buffering mechanisms and may be regulated by calmodulin-specific processes. CDI provides a means for the rate of spontaneous transmitter release to be adjusted to variations in hair cell resting potential and steady state calcium influx.

scholarly journals Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle

Theranostics ◽  
2019 ◽  
Vol 9 (19) ◽  
pp. 5517-5531 ◽  
Author(s):  
Scott R. Burks ◽  
Rebecca M. Lorsung ◽  
Matthew E. Nagle ◽  
Tsang-Wei Tu ◽  
Joseph A. Frank
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Focused Ultrasound ◽  
Sodium Currents ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

scholarly journals γ1Subunit Interactions within the Skeletal Muscle L-type Voltage-gated Calcium Channels

2002 ◽  
Vol 278 (2) ◽  
pp. 1212-1219 ◽  
Author(s):  
Jyothi Arikkath ◽  
Chien-Chang Chen ◽  
Christopher Ahern ◽  
Valérie Allamand ◽  
Jason D. Flanagan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

scholarly journals Structural insights into binding of STAC proteins to voltage-gated calcium channels

2017 ◽  
Vol 114 (45) ◽  
pp. E9520-E9528 ◽  
Author(s):  
Siobhan M. Wong King Yuen ◽  
Marta Campiglio ◽  
Ching-Chieh Tung ◽  
Bernhard E. Flucher ◽  
Filip Van Petegem
Keyword(s):  
Skeletal Muscle ◽  
Native American ◽  
Calcium Channels ◽  
Sh3 Domains ◽  
Mechanical Coupling ◽  
Voltage Gated ◽  
Ec Coupling ◽  
Voltage Gated Calcium Channels ◽  
Disease Variant ◽  
Structural Insights

Excitation–contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different CaVisoforms as a binding site for the SH3 domains and report a crystal structure of the complex with the STAC2 isoform. The interaction site includes the location for a disease variant in STAC3 that has been linked to Native American myopathy (NAM). Introducing the mutation does not cause misfolding of the SH3 domains, but abolishes the interaction. Disruption of the interaction via mutations in the II–III loop perturbs skeletal muscle EC coupling, but preserves the ability of STAC3 to slow down inactivation of CaV1.2.

scholarly journals Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle

Theranostics ◽  
2022 ◽  
Vol 12 (3) ◽  
pp. 1341-1341
Author(s):  
Scott R. Burks ◽  
Rebecca M. Lorsung ◽  
Matthew E. Nagle ◽  
Tsang-Wei Tu ◽  
Joseph A. Frank
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Focused Ultrasound ◽  
Sodium Currents ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

scholarly journals Voltage-gated calcium channels: Their discovery, function and importance as drug targets

2018 ◽  
Vol 2 ◽  
pp. 239821281879480 ◽  
Author(s):  
Annette C. Dolphin
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Drug Targets ◽  
Single Channel ◽  
Calcium Currents ◽  
Kinetic Properties ◽  
Subcellular Localisation ◽  
Channel Blockers ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

This review will first describe the importance of Ca2+ entry for function of excitable cells, and the subsequent discovery of voltage-activated calcium conductances in these cells. This finding was rapidly followed by the identification of multiple subtypes of calcium conductance in different tissues. These were initially termed low- and high-voltage activated currents, but were then further subdivided into L-, N-, PQ-, R- and T-type calcium currents on the basis of differing pharmacology, voltage-dependent and kinetic properties, and single channel conductance. Purification of skeletal muscle calcium channels allowed the molecular identification of the pore-forming and auxiliary α2δ, β and ϒ subunits present in these calcium channel complexes. These advances then led to the cloning of the different subunits, which permitted molecular characterisation, to match the cloned channels with physiological function. Studies with knockout and other mutant mice then allowed further investigation of physiological and pathophysiological roles of calcium channels. In terms of pharmacology, cardiovascular L-type channels are targets for the widely used antihypertensive 1,4-dihydropyridines and other calcium channel blockers, N-type channels are a drug target in pain, and α2δ-1 is the therapeutic target of the gabapentinoid drugs, used in neuropathic pain. Recent structural advances have allowed a deeper understanding of Ca2+ permeation through the channel pore and the structure of both the pore-forming and auxiliary subunits. Voltage-gated calcium channels are subject to multiple pathways of modulation by G-protein and second messenger regulation. Furthermore, their trafficking pathways, subcellular localisation and functional specificity are the subjects of active investigation.

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