ATP‐sensitive potassium (KATP) channels are composed of pore‐forming Kir6.2 and regulatory SUR subunits. A truncated isoform of Kir6.2, Kir6.2ΔC26, forms ATP‐sensitive channels in the absence of SUR1, suggesting the ATP‐inhibitory site lies on Kir6.2.
Previous studies have shown that mutation of the lysine residue at position 185 (K185) in the C‐terminus of Kir6.2 to glutamine, decreased the channel sensitivity to ATP without affecting the single‐channel conductance or the intrinsic channel kinetics. This mutation also impaired 8‐azido[32P]‐ATP binding to Kir6.2.
To determine if K185 interacts directly with ATP, we made a range of mutations at this position, and examined the effect on the channel ATP sensitivity by recording macroscopic currents in membrane patches excised from Xenopus oocytes expressing wild‐type or mutant Kir6.2ΔC26.
Substitution of K185 by a positively charged amino acid (arginine) had no substantial effect on the sensitivity of the channel to ATP. Mutation to a negatively charged residue markedly decreased the channel ATP sensitivity: the Ki for ATP inhibition increased from 85 μM to >30 mM when arginine was replaced with aspartic acid. Substitution of neutral residues had intermediate effects.
The inhibitory effects of ADP, ITP and GTP were also reduced when K185 was mutated to glutamine or glutamate.
The results indicate that a positively charged amino acid at position 185 is required for high‐affinity ATP binding to Kir6.2. Our results demonstrate that ATP does not interact with the side‐chain of K185. It remains unclear whether ATP interacts with the backbone of this residue, or whether its mutation influences ATP binding allosterically.
BACKGROUND
VYC-12 is a novel hyaluronic acid–based dermal filler designed to treat fine lines and improve skin quality. A specialist digital camera and proprietary Digital Analysis of the Cutaneous Surface (DACS) software have previously been used to objectively measure changes in skin features.
OBJECTIVE
To assess the effect of facial treatment with VYC-12 on skin texture using the specialist camera.
MATERIALS AND METHODS
This was a prospective, open-label, 2-center study of 40 women aged 35 to 60 years treated with multiple, microdepot intradermal injections of VYC-12 (2 mL in the face; 1 mL in the neck if required). Eight patients (20.0%) required a touch-up at Day 45. Images were acquired using the specialist camera at baseline and 45 days and 6 months after treatment, and were analyzed by DACS. Clinical improvements were also assessed subjectively using the Global Aesthetic Improvement Scale (GAIS).
RESULTS
VYC-12 improved skin texture from baseline after 45 days (mean improvement: 25.9% ± 9.2%) and 6 months (mean improvement: 30.7% ± 18.2%). Improvements were also evident using the GAIS. There were no major adverse events.
CONCLUSIONS
VYC-12 improves skin quality, as measured using an objective, fast, and reproducible measuring tool. VYC-12 represents a valuable addition to the treatment armamentarium.
BACKGROUND VYC-12 is a hyaluronic acid filler with low cohesivity. OBJECTIVE To evaluate the safety and effectiveness of VYC-12 for aesthetic improvement of horizontal neck lines. METHODS This was a prospective study of consecutive women undergoing neck treatment using VYC-12. All had a baseline score of 1 to 4 on the Allergan Transverse Neck Lines Scale (ATNLS). Individuals with an ATNLS score of 1 to 3 were treated with VYC-12 alone; those with a score of 4 received filler combined with high-intensity focused ultrasound (HIFU). Total VYC-12 volumes were ;1 mL per patient. Follow-up lasted #30 months. RESULTS Fifty women were enrolled (mean age: 55.0 6 5.7 years; n 5 42 VYC-12 alone, n 5 8 VYC-12 + HIFU). Forty-six patients (92%) achieved a $ 1-grade improvement on ATNLS 1 month post-treatment; the mean ATNLS score decreased from 2.64 6 0.83 to 1.44 6 0.81 (p , .0001). Rasch-transformed scores on the FACE-Q "Appraisal of the Neck" questionnaire improved from 31.0 6 14.2 at baseline to 49.7 6 14.4 at 1 month (p , .0001). Repeat injections at 9-to 12-month intervals led to progressive improvements. There were no treatment-related adverse events. CONCLUSION Treatment of the neck using VYC-12 was safe and effective in reducing the appearance of horizontal lines.
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