Inhibition of skeletal muscle CLC-1 chloride channels by low intracellular pH and ATP

Skeletal muscle acidosis during exercise has long been thought to be a cause of fatigue, but recent studies have shown that acidosis maintains muscle excitability and opposes fatigue by decreasing the sarcolemmal chloride conductance. ClC-1 is the primary sarcolemmal chloride channel and has a clear role in controlling muscle excitability, but recombinant ClC-1 has been reported to be activated by acidosis. Following our recent finding that intracellular ATP inhibits ClC-1, we investigated here the interaction between pH and ATP regulation of ClC-1. We found that, in the absence of ATP, intracellular acidosis frompH 7.2 to 6.2 inhibited ClC-1 slightly by shifting the voltage dependence of common gating to more positive potentials, similar to the effect of ATP. Importantly, the effects of ATP and acidosis were cooperative, such thatATPgreatly potentiated the effect of acidosis. Adenosine had a similar effect to ATP at pH 7.2, but acidosis did not potentiate this effect, indicating that the phosphates of ATP are important for this cooperativity, possibly due to electrostatic interactions with protonatable residues of ClC-1. A protonatable residue identified by molecular modeling, His-847, was found to be critical for both pH and ATP modulation and may be involved in such electrostatic interactions. These findings are now consistent with, and provide a molecular explanation for, acidosis opposing fatigue by decreasing the chloride conductance of skeletal muscle via inhibition of ClC-1. The modulation of ClC-1 by ATP is a key component of this molecular mechanism

Intranasal Inhalation of Oxytocin Improves Face Processing in Developmental Prosopagnosia

Developmental prosopagnosia (DP) is characterised by a severe, lifelong impairment in face recognition. Little work has attempted to improve face processing in these individuals, but intriguingly, recent evidence suggests oxytocin can improve face processing in both healthy participants and individuals with autism. This study examined whether oxytocin could also improve face processing in individuals with DP. Ten adults with the condition and 10 matched controls were tested using a randomized placebo-controlled double-blind within-subject experimental design (AB-BA). Each participant took part in two testing sessions where they inhaled 24IU of oxytocin or placebo spray and completed two face processing tests: one assessing face memory and the other face perception. Results showed main effects of both participant group and treatment condition in both face processing tests, but the two did not interact. Specifically, the performance of DP participants was significantly lower than control performance under both oxytocin and placebo conditions, but oxytocin improved processing to a similar extent in both groups

Steady-state magneto-optical trap of fermionic strontium on a narrow-line transition

A steady-state magneto-optical trap (MOT) of fermionic strontium atoms operating on the 7.5 kHz-wide ${^1\mathrm{S}_0} - {^3\mathrm{P}_1}$ transition is demonstrated. This MOT features $8.4 \times 10^{7}$ atoms, a loading rate of $1.3\times 10^{7}$atoms/s, and an average temperature of 12 $\mu$K. These parameters make it well suited to serve as a source of atoms for continuous-wave superradiant lasers operating on strontium's mHz-wide clock transition. Such lasers have only been demonstrated using pulsed Sr sources, limiting their range of applications. Our MOT makes an important step toward continuous operation of these devices, paving the way for continuous-wave active optical clocks.Comment: 11 pages, 7 figure