- 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.
- 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.
- The mechanism of SR Ca2+ leak in CPVT
The K4750Q mutation in ryanodine receptor 2 causes severe catecholaminergic polymorphic ventricular tachycardia. Uehara et al. reveal extensive Ca2+ leak through this mutant receptor and show it is caused by altered gating kinetics, increased Ca2+ sensitivity, and the absence of Ca2+-dependent inactivation.
- 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.
- 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.
- 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.