Specific gating effects of Timothy syndrome CaV1.2 channel mutations determine cardiovascular versus nervous system deficits.
Human mutations in CaV1.2 underlie life-threatening arrhythmias and neurodevelopmental disorders. Through in-depth biophysical analysis, this study identifies divergent mechanistic alterations linked to CaV1.2 channelopathies and reveals an association between changes in channel function and patient phenotypes.
Mutations within the selectivity filter reveal that Kv1 channels have distinct propensities to slow inactivate
Slow inactivation in Kv channels is a mechanism of short-term memory wherein the availability of conducting channels depends on recent channel activity. Here, we compare how mutations near the selectivity filter influence slow inactivation in Shaker and Kv1.2 channels and find that Kv1.2 channels are less prone to inactivate compared with Shaker, yet support common mechanisms of inactivation in the two channels.
Nerve-dependent distribution of subsynaptic type 1 inositol 1,4,5-trisphosphate receptor at the neuromuscular junction
The present study reports on a novel effect of denervation at the neuromuscular junction level. It shows that the absence of nerve causes a reduction in the subsynaptic type 1 inositol 1,4,5-trisphosphate-stained region likely involved in the stabilization of the endplate.
Tsuboi et al. analyze skeletal myocytes from R2509C-RYR1 mice. They find depressed Ca2+ transients, increased resting [Ca2+]cyt, and shortened sarcomeres to the A-band length in homozygous myocytes.