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potassium inwardly-rectifying channel, subfamily J, member 12
KCNJ12 (also known as IRK2; hIRK; hIRK1; KCNJN1; Kir2.2; Kir2.2v; kcnj12x; FLJ14167; hkir2.2x) encodes the inwardly rectifying K+ channel Kir2.2, subfamily J, member 12, which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17.
Kcnj12 : potassium inwardly-rectifying channel, subfamily J, member 12
Interestingly, Kir2.1 and Kir2.2 were significantly more strongly inhibited by cholesterol than Kir2.3, whereas Kir2.4 had intermediate cholesterol sensitivity. This result implies that structural differences between the channels are important for their cholesterol sensitivity. The overall homology between Kir2.1/Kir2.2 and Kir2.3 channels is 60–70%, and several regulatory sites were found to be different in these channels 
High-potency block by extracellular Ba2+ is a striking pharmacological property of IK1 (Schram ). Kir2-based channels have different sensitivities to Ba2+ (Liu , Preisig-Mueller , Schram , Lopatin ). Kir2.2 sensitivity to Ba2+ was similar to cardiac IK1, but the blocking kinetics of Kir2.2 were faster than those of IK1. Currents resulting from co-expression of Kir2 subunits had similar Ba2+ sensitivities and blocking kinetics among groups and were similar to IK1 in both Ba2+ sensitivity and blocking kinetics. Schram 
In light of the different Ba2+ sensitivities of rainbow trout (om)Kir2.1 and omKir2.2 channels, it is concluded that warm acclimation increases either number or activity of the omKir2.2 channels in trout ventricular myocytes. The functional changes in IK1 are independent of omKir2 transcript levels, which remained unaltered by thermal acclimation. Collectively, these findings suggest that thermal acclimation modifies functional properties and subunit composition of the trout Kir2 channels, which may be needed for regulation of cardiac excitability at variable temperatures. Hassinen 
In oocytes using the two electrode voltage clamp technique, potassium currents of hminK-, HERG- and Kir2.2-expressing oocytes were inhibited by pentobarbital with IC50 values of 0.20, 1.58 and 0.54 mM, respectively. Bachmann 
Synapsed Associated Protein SAP97
The strong inwardly rectifying potassium channels Kir2.x are involved in maintenance and control of cell excitability. Recent studies reveal that the function and localization of ion channels are regulated by interactions with members of the membrane-associated guanylate kinase (MAGUK) protein family. To identify novel interacting MAGUK family members, we constructed GST-fusion proteins with the C termini of Kir2.1, Kir2.2 and Kir2.3. GST affinity-pulldown assays from solubilized rat cerebellum and heart membrane proteins revealed an interaction between all three Kir2.x C-terminal fusion proteins and the MAGUK protein synapse-associated protein 97 (SAP97). A truncated form of the C-terminal GST-Kir2.2 fusion protein indicated that the last three amino acids (S-E-I) are essential for association with SAP97. Affinity interactions using GST-fusion proteins containing the modular domains of SAP97 demonstrate that the second PSD-95/Dlg/ZO-1 (PDZ) domain is sufficient for interaction with Kir2.2. Coimmunoprecipitations demonstrated that endogenous Kir2.2 associates with SAP97 in rat cerebellum and heart. Additionally, phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97. In rat cardiac ventricular myocytes, Kir2.2 and SAP97 colocalized in striated bands corresponding to T-tubules 
Carbonyl Cyanide/P-trifluoromethoxyphenlydrazone (FCCP) and sodium azide are all known inhibitors of Kir2 inward rectifiers 
Crystal Structure of Kir2.2
We present the crystal structure of Kir2.2 from chicken, which, excluding the unstructured amino and carboxyl termini, is 90% identical to human Kir2.2. Crystals containing rubidium (Rb+), strontium (Sr2+), and europium (Eu3+) reveal binding sites along the ion conduction pathway that are both conductive and inhibitory. The sites correlate with extensive electrophysiological data and provide a structural basis for understanding rectification. The channel's extracellular surface, with large structured turrets and an unusual selectivity filter entryway, might explain the relative insensitivity of eukaryotic inward rectifiers to toxins 
Expression of Kir2
Three poreforming a-subunits of the Kir2 family, Kir2.1–3, are expressed in cardiomyocytes (Liu ). In the human heart, Kir2.1 transcripts are 10-fold more abundant than those of Kir2.2 or Kir2.3 (Wang ). The relative expression of Kir2 transcripts fails to explain a variety of cardiac IK1 properties (Wang ).
Rat brain endothelial cells express Kv1 and Kir2 K+ channels. Millar 
Cardiac Function of Kir2.2
Cardiac potassium currents - which are partly mediated by Kir2.2 - are critical for regulation of resting conductance and action potential repolarization. The late phase of the action potential repolarization in cardiomyocytes is initiated in most species by activation of the delayed rectifier potassium current (IK) which consists of two components (Sanguinetti and Jurkiewicz 1990 ): a rapidly activating component (IKr) and a slowly activating component (IKs). Inward rectifier current (IK1) is the major current at the resting membrane potential (RMP) of atrial and ventricular myocytes, and contributes to the final stages of membrane repolarization. Bachmann 
Vascular Tone in Mice Cerebral Artery
experiments that compared arteries from Kir2.2 knockout with control arteries failed to identify any differences. Both sets of adult vessels exhibited similar pressure-induced constrictions and both dilated when exposed to an external solution that contained 15 mmol/L K+ or to 0 mmol/L Ca2+. Thus, it is unlikely that the Kir2.2 gene plays a role similar to that of Kir2.1 in the regulation of vascular tone 
Different ratios of the expression of Kir2.1 - Kir2.3 is potentially contributing to phenotypic diversity in Andersen’s syndrome (Preisig -Mueller ).
Kir channels contribute to a wide variety of physiological functions such as vascular tone, heart rate, glial buffering of potassium, renal salt flow and insulin release (Isomoto et al., 1997; Nichols and Lopatin, 1997; Vandenberg, 1994). The classical strong Kir channels, Kir2.1, Kir2.2 and Kir2.3, are important in the modulation of cell excitability, repolarization of the action potential and determination of the cellular resting potential 
Kir2.2 Kinetics compared with Kir2.1
we have implemented a concatemeric approach, whereby all four cloned Kir2 subunits were linked in tandem, in order to study the effects of Kir2.1 and Kir2.2 heteromerization on properties of the resulting channels. Kir2.2 subunits contributed stronger to single-channel conductance than Kir2.1 subunits, and channels containing two or more Kir2.2 subunits displayed conductances indistinguishable from that of a Kir2.2 homomeric channel. In contrast, single-channel kinetics was a more discriminating property. The open times were significantly shorter in Kir2.2 channels compared with Kir2.1 channels and decreased nearly proportionally to the number of Kir2.2 subunits in the heteromeric channel. Similarly, the sensitivity to block by barium also depended on the proportions of Kir2.1 to Kir2.2 subunits. Overall, the results showed that Kir2.1 and Kir2.2 subunits exert neither a dominant nor an anomalous effect on any of the properties of heteromeric channels 
Single Channel Conductance of Kir2.2 in HEK 293 Cells
Human Kir2.2 recorded in X.oocytes
A standardised voltage protocol was used in all measurements of this study to elicit characteristic inwardly rectifying Kir2.2 currents: test pulses to potentials ranging from −120 to +40 mV were applied in 10 mV increments (400 ms). The holding potential was −80 mV. At potentials below the potassium reversal potential of approximately −80 mV under the given experimental conditions, Kir2.2 channels generated large inward currents.