G-proteingated rectifying K-channel 2

G protein-gated inwardly rectifying potassium (GIRK) channels hyperpolarize neurons in response to activation of many G-protein coupled receptors and control the excitability of neurons at post synaptic terminals through GIRK-mediated self-inhibition, slow synaptic potentials and volume transmission. GIRK channel functioning and trafficking are highly dependent on their subunit composition. GIRK activity has an important role in physiological responses, including pain perception and memory modulation. Abnormal GIRK function has been implicated in altering neuronal excitability and cell death that may be important in the pathophysiology of human diseases such as epilepsy, Down’s syndrome, Parkinson’s disease and drug addiction.(1). GIRK channels are expressed in the brain, heart, skeletal muscle, and endocrine tissue. GIRK channels are members of the super-family of proteins known as inward rectifier K+ (Kir) channels that function to stabilize the cell resting membrane potential near the K+ equilibrium potential (EK). These channels generate slow inhibitory postsynaptic potentials following the activation of Gi/o-protein-coupled receptors .The major role of the GIRK channels is to mediate inhibitory responses in the nervous system by decreasing neuronal excitability. GIRK channels also play role at presynaptic sites due to their localization in axon terminals. A major G protein-coupled receptor activating postsynaptic GIRK channels is the metabotropic γ-aminobutyric acid (_B) (GABA_B) receptor. GIRK channel-mediated inhibition of glutamate release occurs through GABA_B receptors in the cerebral cortex. Four different cDNAs encode GIRK channel subunits in mammals (GIRK1–4) and they combine to form functional homomeric as well as heteromeric channels. In central neurons most neuronal GIRK channels are heteromeric complexes containing both GIRK1 and GIRK2. (2).

GIRK2 has its highest expression in hippocampus, which along with other inhibitory neurotransmitters, such as GABA, serotonin, adenosine and somatostatin, stimulate their cognate G protein coupled receptors(GPCRs) leading to hyperpolarization of the neuron’s membrane potential. GABA_B receptors and GIRK channels are colocalized in dendritic spines. Loss of GIRK2 signaling leads to impairments in learning and memory tasks, changes in the response to drugs of abuse and alcohol, while excessive GIRK activity may interfere with neuronal signaling, such as in Down’s syndrome. Differential expression of GIRK channels in dendritic shafts and spines lead to alterations in synaptic plasticity and changes localization of GIRK channels in hippocampal neurons. Morphine alters GIRK signaling in hippocampal neurons. (3) A gene encoding GIRK2 has been found within the so-called Down Syndrome critical region (DSCR) of Chr. 21. It is the only known channel-coding gene from genetically defined DSCR that is highly expressed in the central nervous system (CNS). (4) Opioid ligands bind to opioid receptors, and the signal is transmitted to a variety of effectors e.g., adenylate cyclase, calcium ion channels, and GIRK, thereby resulting in analgesic effects (5)

The GIRK2-selective antibodies were generated using a peptide selected form a region between amino acids 4-20.  The GIRK2 antibodies are affinity purified over immobilized antigen based affinity chromatography, and the purified immunoglobulins are stabilized in antibody stabilization buffer for long-term storage.  FabGennix Int. Inc. will provide limited quantities of antigenic blocking peptides for competition assays involving GIRK2 antibody. Antibodies to GIRK2 label ~52kDa protein in Western blot positive control and several other tissues.  FabGennix Inc. will conjugate this and other antibodies from its catalog to either secondary enzymes (alk-Pase or HRP) or fluorescent probes at a nominal cost upon request.  FabGennix also provides custom antibody production services for researchers that are looking for high affinity mono and polylconal antibodies in various species. We specialize in making application specific antibodies that are useful in IHC, confocal and other applications where native antigen is detected. For a complete listing of all FabGennix antibodies please visit www.Fabgennix.com.

For research use only, not for diagnostic or therapeutic use.