Background:There is an ongoing debate whether patients with constitutional varus should be restored to neutral mechanical alignment following total knee arthroplasty (TKA).Objective:The aim of this retrospective cohort study is to determine whether mild unintentional postoperative varus alignment (3°–6°) influences TKA outcome in patients with and without preoperative varus alignment due to medial osteoarthritis of the knee.Methods:We analyzed 172 consecutive TKA cases between April 2011 and May 2014. Patients were divided into four groups based on their preoperative and postoperative hip-knee-ankle angles (HKA): preoperative varus ≤ 3° with postoperative varus position ≤ 3° (Group 1, n = 47); preoperative varus >3° with postoperative varus ≤ 3° (Group 2, n = 104); preoperative varus ≤ 3° with postoperative varus malalignment > 3° (Group 3, n = 3); and preoperative varus > 3° with postoperative varus malalignment > 3° (Group 4, n = 18). Patients were followed up until 2 years postoperatively.Results:Knee Society Score and Western Ontario and McMaster University Osteoarthritis Index scores for all study groups increased following TKA, with no postoperative differences at any time point. Group 4 performed significantly better on the Forgotten Joint Score than Group 2 (p = 0.019). Group 4 performed significantly better on the High Flexion Knee Score than Group 2 (p = 0.004) and Group 1 (p = 0.019). All other between-group differences were not statistically significant.Conclusion:Residual postoperative varus alignment of the lower limb does not appear to adversely affect clinical outcome following TKA for varus-type osteoarthritis.

Large-conductance Ca(2+) -activated (BK) potassium channels are centrally involved in neurovascular coupling, immunity, and neural transmission. The ability to be synergistically activated by membrane depolarization, different ligands and intracellular Ca(2+) links intracellular signaling and membrane excitability. The diverse physiological functions of BK channels crucially depend on regulatory β subunits. Although first studies characterized the neuronal distribution of BKβ subunits in the rodent brain, it is largely unknown which β subunit proteins are expressed in astrocytes and thus mediate these regulatory effects. We therefore analyzed the expression of BKβ subunits in rat and mouse brain and glial cell cultures. A monospecific polyclonal antibody against the BKβ4 channel subunit was raised, affinity-purified and extensively characterized. BKβ4 and to a lesser degree BKβ1 transcripts and protein were detected in several astrocytic populations and cultured cells. Particularly strong BKβ4 immunostaining was detected in astrocytic progenitors derived from the subventricular zone. The overlapping expression of BKα and BKβ4 in astrocytes implies a functional relationship and suggests that BKβ4 is an important accessory β subunit for astrocytic BK channels. In addition, BKβ4 might exert effects independent of the α subunit as functional heterologous co-expression of Nav1.6 and BKβ4 resulted in reduced Nav1.6 sodium currents. Thus, BKβ4 expression in astrocytes likely participates in regulating astrocytic voltage gradients and maintaining K(+) homeostasis, hence enabling astrocytes to fulfill their complex regulatory influence on proper brain function.

Large conductance Ca(2+)-activated BK channels are important regulators of action potential duration and firing frequency in many neurons. As the pore-forming subunits of BK channels are encoded by a single gene, channel diversity is mainly generated by alternative splicing and interaction with auxiliary beta-subunits (BKbeta1-4). In hypothalamic neurons several BK channel subtypes have been described electrophysiologically; however, the distribution of BKbeta subunits is unknown so far. Therefore, an antibody against the large extracellular loop of the BKbeta1 subunit was raised, freed from cross-reactivity against BKbeta2-4 and affinity-purified. The resulting polyclonal monospecific BKbeta1 antibody was characterized by Western blot analysis, ELISA techniques and immunocytochemical staining of BKbeta1-4-transfected CHO and COS-1 cells. Regional and cellular distribution in the rat hypothalamus was analysed by immunocytochemistry and in situ hybridization experiments. Immunocytochemical staining of rat hypothalamic neurons indicates strong BKbeta1 expression in the supraoptic nucleus and the magno- and parvocellular parts of the paraventricular nucleus. Lower expression was found in periventricular nucleus, the arcuate nucleus and in the median eminence. Immunostaining was predominantly localized to somata. In addition, pericytes and ependymal epithelial cells showed BKbeta1 labelling. In all cases immunocytochemical results were supported by in situ hybridization.