gamma1-dependent down-regulation of recombinant voltage-gated Ca2+ channels. 2007

Alejandro Sandoval, and Jyothi Arikkath, and Eduardo Monjaraz, and Kevin P Campbell, and Ricardo Felix
.Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute Cinvestav-IPN, Avenida IPN 2508, Colonia Zacatenco, Mexico City, DF CP 07300, Mexico.

(1) Voltage-gated Ca2+ (CaV) channels are multi-subunit membrane complexes that allow depolarization-induced Ca2+ influx into cells. The skeletal muscle L-type CaV channels consist of an ion-conducting CaV1.1 subunit and auxiliary alpha2delta-1, beta1 and gamma1 subunits. This complex serves both as a CaV channel and as a voltage sensor for excitation-contraction coupling. (2) Though much is known about the mechanisms by which the alpha2delta-1 and beta1 subunits regulate CaV channel function, there is far less information on the gamma1 subunit. Previously, we characterized the interaction of gamma1 with the other components of the skeletal CaV channel complex, and showed that heterologous expression of this auxiliary subunit decreases Ca2+ current density in myotubes from gamma1 null mice. (3) In the current report, using Western blotting we show that the expression of the CaV1.1 protein is significantly lower when it is heterologously co-expressed with gamma1. Consistent with this, patch-clamp recordings showed that transient transfection of gamma1 drastically inhibited macroscopic currents through recombinant N-type (CaV2.2/alpha2delta-1/beta3) channels expressed in HEK-293 cells. (4) These findings provide evidence that co-expression of the auxiliary gamma1 subunit results in a decreased expression of the ion-conducting subunit, which may help to explain the reduction in Ca2+ current density following gamma1 transfection.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001464 Barium An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D018408 Patch-Clamp Techniques An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. Patch Clamp Technique,Patch-Clamp Technic,Patch-Clamp Technique,Voltage-Clamp Technic,Voltage-Clamp Technique,Voltage-Clamp Techniques,Whole-Cell Recording,Patch-Clamp Technics,Voltage-Clamp Technics,Clamp Technique, Patch,Clamp Techniques, Patch,Patch Clamp Technic,Patch Clamp Technics,Patch Clamp Techniques,Recording, Whole-Cell,Recordings, Whole-Cell,Technic, Patch-Clamp,Technic, Voltage-Clamp,Technics, Patch-Clamp,Technics, Voltage-Clamp,Technique, Patch Clamp,Technique, Patch-Clamp,Technique, Voltage-Clamp,Techniques, Patch Clamp,Techniques, Patch-Clamp,Techniques, Voltage-Clamp,Voltage Clamp Technic,Voltage Clamp Technics,Voltage Clamp Technique,Voltage Clamp Techniques,Whole Cell Recording,Whole-Cell Recordings
D018482 Muscle, Skeletal A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles

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