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Background: Many hand surgeons prefer to close palmar wounds with non-absorbable mattress sutures. Suture removal can be painful and time-consuming. In this study, we investigated if suture removal can be facilitated by including a vessel loop in wound closure following open carpal tunnel release (CTR). Methods: Overall, 47 patients aged 18 to 75 undergoing elective primary open unilateral CTR completed this unblinded, prospective randomized controlled superiority trial. Subjects were randomized into 1 of 2 study arms: (1) wound closure without a vessel loop (standard, n = 28); or (2) wound closure with a vessel loop (vessel loop, n = 19). Data were collected on time for wound closure and for suture removal. A visual analog scale (VAS) was used to assess satisfaction and pain with suture removal. Results: There were no significant differences between the 2 groups in patient demographics or time for suture placement. Visual analog scale satisfaction with suture removal was significantly lower in the standard group (8.6 ± 2.6) compared to vessel loop group (9.9 ± 0.28, P <.05). VAS pain with suture removal was significantly higher in the standard group (2.6 ± 2.7) versus vessel loop group (0.68 ± 1.1, P <.01). Additionally, suture removal time was significantly longer in standard group (84 seconds ± 83) versus vessel loop group (31 seconds ± 13, P <.0001). Conclusions: Addition of a vessel loop in wound closure for primary open CTR increases patient satisfaction and reduces pain with and time taken for suture removal. [ABSTRACT FROM AUTHOR]

Key points The cytosolic K+ channel accessory subunit, K+ channel interacting protein 2 (KChIP2), was previously suggested to be critical in the generation of cardiac fast transient outward current ( Ito,f) channels., The experiments presented here revealed the novel finding that targeted deletion of KChIP2 results in the complete loss of the Kv4.2 protein, although Kcnd2 (Kv4.2) transcript expression is not decreased in KChIP2−/− ventricles., In contrast, the slow transient outward current, Ito,s, is increased in KChIP2−/− left ventricular apex myocytes and ventricular action potential waveforms in KChIP2−/− and WT mice are not significantly different., These results demonstrate the critical role of KChIP2 in the stabilization of native Kv4 proteins and that the loss of the Kv4.2 protein underlies the elimination of Ito,f in KChIP2−/− myocytes., Taken together, the results here demonstrate that electrical remodelling compensates for the elimination of Ito,f, maintaining physiological action potential repolarization in mouse myocardium., Abstract The fast transient outward K+ current ( Ito,f) underlies the early phase of myocardial action potential repolarization, contributing importantly to the coordinated propagation of activity in the heart and to the generation of normal cardiac rhythms. Native Ito,f channels reflect the tetrameric assembly of Kv4 pore-forming (α) subunits, and previous studies suggest roles for accessory and regulatory proteins in controlling the cell surface expression and the biophysical properties of Kv4-encoded Ito,f channels. Here, we demonstrate that the targeted deletion of the cytosolic accessory subunit, K+ channel interacting protein 2 (KChIP2), results in the complete loss of the Kv4.2 protein, the α subunit critical for the generation of mouse ventricular Ito,f. Expression of the Kcnd2 (Kv4.2) transcript in KChIP2−/− ventricles, however, is unaffected. The loss of the Kv4.2 protein results in the elimination of Ito,f in KChIP2−/− ventricular myocytes. In parallel with the elimination of Ito,f, the slow transient outward K+ current ( Ito,s) is upregulated and voltage-gated Ca2+ currents ( ICa,L) are decreased. In addition, surface electrocardiograms and ventricular action potential waveforms in KChIP2−/− and wild-type mice are not significantly different, suggesting that the upregulation of Ito,s and the reduction in ICa,L compensate for the loss of Ito,f. Additional experiments revealed that Ito,f is not 'rescued' by adenovirus-mediated expression of KChIP2 in KChIP2−/− myocytes, although ICa,L densities are increased. Taken together, these results demonstrate that association with KChIP2 early in the biosynthetic pathway and KChIP2-mediated stabilization of Kv4 protein are critical determinants of native cardiac Ito,f channel expression. [ABSTRACT FROM AUTHOR]

Abstract: Considerable evidence indicates that native neuronal voltage-gated K+ (Kv) currents reflect the functioning of macromolecular Kv channel complexes, composed of pore-forming (α)-subunits, cytosolic and transmembrane accessory subunits, together with regulatory and scaffolding proteins. The individual components of these macromolecular complexes appear to influence the stability, the trafficking, the localization and/or the biophysical properties of the channels. Recent studies suggest that Kv channel accessory subunits subserve multiple roles in the generation of native neuronal Kv channels. Additional recent findings suggest that Kv channel accessory subunits can respond to changes in intracellular Ca2+ or metabolism and thereby integrate signaling pathways to regulate Kv channel expression and properties. Although studies in heterologous cells have provided important insights into the effects of accessory subunits on Kv channel expression/properties, it has become increasingly clear that experiments in neurons are required to define the physiological roles of Kv channel accessory and associated proteins. A number of technological and experimental hurdles remain that must be overcome in the design, execution and interpretation of experiments aimed at detailing the functional roles of accessory subunits and associated proteins in the generation of native neuronal Kv channels. With the increasing association of altered Kv channel functioning with neurological disorders, the potential impact of these efforts is clear. [Copyright &y& Elsevier]

The rapidly activating and inactivating voltage-dependent outward K+ (Kv) current, IA, is widely expressed in central and peripheral neurons. IA has long been recognized to play important roles in determining neuronal firing properties and regulating neuronal excitability. Previous work demonstrated that Kv4.2 and Kv4.3-1 subunits are the primary determinants of IA in mouse cortical pyramidal neurons. Accumulating evidence indicates that native neuronal Kv4 channels function in macromolecular protein complexes that contain accessory subunits and other regulatory molecules. The K+ channel interacting proteins (KChIPs) are among the identified Kv4 channel accessory subunits and are thought to be important for the formation and functioning of neuronal Kv4 channel complexes. Molecular genetic, biochemical, and electrophysiological approaches were exploited in the experiments described here to examine directly the roles of KChIPs in the generation of functional Kv4-encoded IA channels. These combined experiments revealed that KChIP2, KChIP3, and KChIP4 are robustly expressed in adult mouse posterior (visual) cortex and that all three proteins coimmunoprecipitate with Kv4.2. In addition, in cortical pyramidal neurons from mice lacking KChIP3 (KChIP3/), mean IA densities were reduced modestly, whereas in mean IA densities in KChIP2/andWTneurons were not significantly different. Interestingly, in both KChIP3/and KChIP2/ cortices, the expression levels of the other KChIPs (KChIP2 and 4 or KChIP3 and 4, respectively) were increased. In neurons expressing constructs to mediate simultaneous RNA interference-induced reductions in the expression of KChIP2, 3, and 4, IA densities were markedly reduced and Kv current remodeling was evident. [ABSTRACT FROM AUTHOR]

Members of the K(+) channel-interacting protein (KChIP) family bind the distal N termini of members of the Shal subfamily of voltage-gated K(+) channel (Kv4) pore-forming (α) subunits to generate rapidly activating, rapidly inactivating neuronal A-type (I(A)) and cardiac transient outward (I(to)) currents. In heterologous cells, KChIP co-expression increases cell surface expression of Kv4 α subunits and Kv4 current densities, findings interpreted to suggest that Kv4·KChIP complex formation enhances forward trafficking of channels (from the endoplasmic reticulum or the Golgi complex) to the surface membrane. The results of experiments here, however, demonstrate that KChIP2 increases cell surface Kv4.2 protein expression (∼40-fold) by an order of magnitude more than the increase in total protein (∼2-fold) or in current densities (∼3-fold), suggesting that mechanisms at the cell surface regulate the functional expression of Kv4.2 channels. Additional experiments demonstrated that KChIP2 decreases the turnover rate of cell surface Kv4.2 protein by inhibiting endocytosis and/or promoting recycling. Unexpectedly, the experiments here also revealed that Kv4.2·KChIP2 complex formation stabilizes not only (total and cell surface) Kv4.2 but also KChIP2 protein expression. This reciprocal protein stabilization and Kv4·KChIP2 complex formation are lost with deletion of the distal (10 amino acids) Kv4.2 N terminus. Taken together, these observations demonstrate that KChIP2 differentially regulates total and cell surface Kv4.2 protein expression and Kv4 current densities.

The rapidly activating and inactivating voltage-dependent outward K(+) (Kv) current, I(A), is widely expressed in central and peripheral neurons. I(A) has long been recognized to play important roles in determining neuronal firing properties and regulating neuronal excitability. Previous work demonstrated that Kv4.2 and Kv4.3 α-subunits are the primary determinants of I(A) in mouse cortical pyramidal neurons. Accumulating evidence indicates that native neuronal Kv4 channels function in macromolecular protein complexes that contain accessory subunits and other regulatory molecules. The K(+) channel interacting proteins (KChIPs) are among the identified Kv4 channel accessory subunits and are thought to be important for the formation and functioning of neuronal Kv4 channel complexes. Molecular genetic, biochemical, and electrophysiological approaches were exploited in the experiments described here to examine directly the roles of KChIPs in the generation of functional Kv4-encoded I(A) channels. These combined experiments revealed that KChIP2, KChIP3, and KChIP4 are robustly expressed in adult mouse posterior (visual) cortex and that all three proteins coimmunoprecipitate with Kv4.2. In addition, in cortical pyramidal neurons from mice lacking KChIP3 (KChIP3(-/-)), mean I(A) densities were reduced modestly, whereas in mean I(A) densities in KChIP2(-/-) and WT neurons were not significantly different. Interestingly, in both KChIP3(-/-) and KChIP2(-/-) cortices, the expression levels of the other KChIPs (KChIP2 and 4 or KChIP3 and 4, respectively) were increased. In neurons expressing constructs to mediate simultaneous RNA interference-induced reductions in the expression of KChIP2, 3, and 4, I(A) densities were markedly reduced and Kv current remodeling was evident.