- Cyclic AMP reverses aging in pacemaker cells
Aging reduces pacemaker activity and shifts the voltage dependence of activation of the funny current, If, in sinoatrial node myocytes. Sharpe et al. find that these effects of aging can be reversed by application of exogenous cAMP but not by stimulation of endogenous cAMP.
- Modulatory role of HOOK region of CaV β subunits
Voltage-gated Ca2+ channels contain β subunits that regulate channel gating. Park et al. conduct a comprehensive analysis of the role of the β subunit HOOK region and show that its B domain is important for PIP2 regulation of channel gating and that its A domain modulates this effect.
- ADPR binding on TRPM2
ADP ribose (ADPR) is an endogenous ligand for the transient receptor potential melastatin 2 (TRPM2) channel. Yu et al. identify 11 residues in the NUDT9 homology domain of TRPM2 that form a binding site for ADPR involving van der Waals, polar solvation, and electronic interactions.
- Intrinsically liganded CNBhD in KCNH activation
hEAG1 is a member of the KCNH family of ion channels, which are characterized by C-terminal regions with homology to cyclic nucleotide–binding domains (CNBhDs). Zhao et al. show that an “intrinsic ligand” occupying the CNBhD binding pocket promotes the activated and open state of the channel.
- CaM regulates Na+ channel persistent current
The molecular mechanisms controlling “persistent” current through voltage-gated Na+ channels are poorly understood. Yan et al. show that apocalmodulin binding to the intracellular C-terminal domain limits persistent Na+ flux and accelerates inactivation across the voltage-gated Na+ channel family.
- Kir6.1 in islet KATP channels
Kir6.2-containing KATP channels are prominent in pancreatic β cells, and gain-of-function mutations in these channels are the most common cause of human neonatal diabetes mellitus. Remedi et al. find that Kir6.1 subunits are also present in pancreatic KATP channels and that gain-of-function mutations can also cause impaired glucose tolerance and insulin secretion.
- Binding curves and parameter identifiability
In their preceding paper, Middendorf and Aldrich describe a method to determine the accuracy of binding parameters estimated from models of agonist binding. Here, they present an approach to determine whether binding parameters can be accurately estimated from experimental, or noisy, data.
- Vesicle recycling in stellate astrocytic processes
Communication between astrocytes and neurons has been difficult to study because cultured astrocytes do not resemble those in vivo. Wolfes et al. develop a stellate astrocyte monoculture with physiological characteristics and find that VAMP2 and SYT7 mark distinct vesicle populations in astrocytes.