Disease relevance of Kcna5

• Exposure to chronic hypoxia decreased mRNA and protein levels of Kv1.1, Kv1.5, Kv1.6, Kv2.1, and Kv4.3 alpha-subunits in dPAs but did not alter gene or protein expression of these channels in aorta [1].
• Regardless of the etiology of the hypertrophy, the amounts of Kv1.4 and Kv1.5 mRNAwere similar in treated, sham and control rats [2].
• In particular, increased Kv1.5 gene expression, having a transient nature, implied the possible biochemical electrical remodeling unique to paroxysmal tachycardia [3].
• T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05) [4].
• RESULTS: MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05) [4].

Psychiatry related information on Kcna5

• 8. In contrast, larger diameter neurons associated with mechanoreception and proprioception express high levels of Kv1.1 and Kv1.2 without Kv1.4 or other Kv1 alpha subunits, suggesting that heteromers of these subunits predominate on large, myelinated afferent axons that extend from these cells [5].
• Our results suggest that Kv1.5 and Kv1.6 Shaker K+ channels play an important role in regulating motor activity that increases in mRNA and protein levels of the spinal cord K+ channels after chronic morphine exposure could be viewed as a cellular adaptation which compensates for a persistent opioid-induced inhibition of K+ channel activity [6].

High impact information on Kcna5

• Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in different ways in the presence and absence of ligands [7].
• Kv1.5 expression was localized less in newborn tissue, with punctate antibody staining dispersed on the myocyte surface [8].
• To determine whether the Kv1.5 isoform plays a role in the cardiac action potential, it is necessary to confirm the expression of this channel in cardiac myocytes [8].
• The cloned Kv1.5 K+ channel displays similar kinetics and pharmacology to a delayed rectifier channel found in atrial myocytes [8].
• While both antichannel antibodies localized the Kv1.5 protein in cardiac myocytes, only the NH2-terminal antibodies stained vascular smooth muscle [8].

Chemical compound and disease context of Kcna5

• Recently, we found that dexamethasone increases expression of Kv1.5 K+ channel mRNA in GH3 rat pituitary tumor cells [9].
• A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum [10].
• Application of 1 microM losartan, an angiotensin II type I receptor blocker, significantly attenuated the FCGM-induced myocyte hypertrophy and reduction of Kv1.5 K+ channel expression [11].
• Propranolol, a beta-adrenergic blocker, did not inhibit the T4-dependent increase in Kv1.5 mRNA, indicating that the increase is not due to the increased beta-adrenergic stimuli under hyperthyroidism [12].
• In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats [13].

Biological context of Kcna5

• A cAMP response element (CRE) consensus signal was identified in the 5'-noncoding region. cAMP regulates the expression of Kv1.5 gene in a cell-specific manner [14].
• Transient transfection assays using 5'-deletion mutations of Kv1.5 5'-flanking sequences revealed that the CRE located at +636 can confer the cAMP inducibility to Kv1.5 reporter gene constructs and binds to CRE-binding protein (CREB) and CRE modulator protein (CREM) in electromobility gel shift assays [14].
• 5. By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern [15].
• Transient transfection experiments in COS-7 cells revealed that SAP97 and Kv1.5 polypeptides formed perinuclear clustered complexes that could be coimmunoprecipitated [16].
• Electrophysiological findings that the shortening of the action potential produced by 4-hour pacing was almost abolished by a low concentration of 4-aminopyridine implied that the increased Kv1.5 protein was functioning [3].

Anatomical context of Kcna5

• By contrast, cotransfected ZO-1 and Kv1.5 polypeptides in COS-7 cells could not be coprecipitated nor did the coinjection of ZO-1 augment the Kv1.5-encoded currents in oocytes [16].
• Collectively, our results suggest that SAP97 may play an important role in the modulation of Kv1.5 channel function in cardiac myocytes [16].
• On the basis of these novel observations, we propose a new model of Kv channel function in arterial smooth muscle in which Kv2 channels (in combination with Kv1 channels) contribute to membrane hyperpolarization and thus oppose constriction [17].
• Immunocytochemistry in cardiac myocytes revealed colocalization of SAP97 and Kv1.5, both at the intercalated disks and the lateral membranes [16].
• Nocodazole pretreatment, which depolymerizes the microtubule cytoskeleton along which dynein tracks, also doubled Kv1.5 currents in HEK cells and sustained K+ currents in isolated rat atrial myocytes [18].

Associations of Kcna5 with chemical compounds

• Heterologously expressed human PASMC Kv1.5 generated an O2- and correolide-sensitive I(K) like that in resistance PASMCs [19].
• These increased currents were blocked by 1 mmol/L 4-aminopyridine, and the specific Kv1.5 antagonist, DMM (100 nM) [18].
• Injection of dexamethasone into adrenalectomized rats acted within a day to increase ventricular Kv1.5 mRNA and immunoreactive protein approximately 50-fold and approximately 20-fold, respectively [20].
• Expression of a C-terminal truncated Kv1.4 subunit, abolishing Kv1 channel family currents, reduced delayed rectifier currents by approximately 25% and enhanced glucose-stimulated insulin secretion from rat islets by 40% [21].
• Furthermore, cardiac myocytes cocultured with cells that endogenously (Mv 1 Lu) or heterologously (Chinese hamster ovary cells) express the receptor-type protein tyrosine phosphatase mu (RPTPmu) display Kv1.5 mRNA levels paralleling that which was observed in myocytes cultured under high-density conditions and in intact tissue [22].

Physical interactions of Kcna5

• SAP97 interacts with Kv1.5 in heterologous expression systems [16].
• Although KChAP binds to Kv1.5, it has no effect on Kv1.5 currents [23].

Regulatory relationships of Kcna5

• Kv beta 1.1 induced inactivation in members of the Kv1 subfamily with the exception of Kv 1.6; no inactivation of Kv 2.1, Kv 3.4 delta 2-28 and Kv4.1 channels could be observed [24].
• The Kv1.5 mRNA level was dramatically repressed while the Kv1.4 mRNA level was remarkably increased [25].
• In contrast to PE, a 48% enhancement of the protein expression of Kv1.5 channel was induced by IGF-1 and this stimulation was specifically blocked by genistein [26].

Other interactions of Kcna5

• The Kv2 mRNA is expressed only in brain, whereas the Kv1 and Kv3 transcripts are found in several other tissues as well [27].
• 1. Anti-Kv1.5 and anti-Kv2.1 caused additive depolarization in resistance PASMCs (Kv1.5>Kv2.1) and inhibited hypoxic depolarization [19].
• There was an approximately twofold decrease in total Kv4 subfamily mRNA expression in atrial muscle relative to ventricular muscle and a 70% increase in total Kv1 subfamily mRNA [28].
• The increase of Kv1.5 and the decrease of Kv4.2 and Kv4.3 mRNA levels were both rate dependent [3].
• The chimaeric beta-subunits (beta 1/ beta 2 and beta 3/ beta 2) induced fast inactivation of several Kv1 channels, indicating that Kv beta 2 associates with these alpha-subunits [24].

Analytical, diagnostic and therapeutic context of Kcna5

• Western blot analysis demonstrated that four I(K)-related Kv channel proteins (Kv1.2, Kv1. 3, Kv1.5, and Kv2.1) were detected in mesenteric artery tissues [29].
• Reduction of endogenous glucocorticoids by adrenalectomy decreased ventricular Kv1.5 mRNA approximately 8-fold, which was estimated by using cyclophilin mRNA as an internal control [20].
• To test whether these steroids might also induce Kv1.5 gene expression in the heart, cardiac channel mRNA and protein were measured by RNase protection assay and by immunoblotting with antibody specific for the extracellular domain of Kv1.5 polypeptide [20].
• The effects of strontium (Sr2+; 7-50 mM) on five different cloned rat K channels (Kv1.1, Kv1.5, Kv1.6, Kv2.1, and Kv3.4), expressed in oocytes of Xenopus laevis, were investigated with a two-electrode voltage clamp technique [30].
• Using immunoprecipitation, we show that Kv1.5 is associated with Src family protein tyrosine kinases and that this association does not change with cell differentiation [31].

References