ON THE COVER
Touch indents and creates mechanical strain in the skin and underlying tissue. Th is strain extends beyond the point of indentation, activating distant mechanoreceptor channels. Here, a Caenorhabditis elegans roundworm expressing a collagen::GFP fusion protein in its skin is shown before (green) and during (magenta) indentation with a black bead. See page 1213.
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Measurement of intracellular ion activity in skeletal muscle fibers: Four microelectrodes or no deal
Allard reviews a new powerful method allowing measurement of intracellular ion activity in isolated skeletal muscle fibers.
Milestones in Physiology
The contribution of voltage clamp fluorometry to the understanding of channel and transporter mechanisms
Cowgill and Chanda discuss the importance of voltage clamp fluorometry to the functional interpretation of ion channel and transporter structures.
Binding and structural asymmetry governs ligand sensitivity in a cyclic nucleotide–gated ion channel
HCN channel opening is facilitated by cyclic nucleotides, but what determines the sensitivity of these channels to cAMP or cGMP is unclear. Ng et al. propose that ligand sensitivity depends on negative cooperativity and the asymmetric effects of ligand binding on channel structure and pore opening.
Through experiment and simulation, Katta et al. reveal that pushing faster and deeper recruits more and more distant mechano-electrical transduction channels during touch. The net result is a dynamic receptive field whose size and shape depends on tissue mechanics, stimulus parameters, and channel distribution within sensory neurons.
G-protein–gated inwardly rectifying potassium channels are important mediators of inhibitory neurotransmission. Based on microsecond-scale molecular dynamics simulations, Bernsteiner et al. propose novel gating details that may enable K+ flux via a direct knock-on mechanism.