Parameter Optimization for Ion Channel Models: Integrating New Data with Known Channel Properties.

Ion channels play a central role in membrane physiology, but to fully understand how they operate, one must have accurate kinetic mechanisms. Estimating kinetics is not trivial when the mechanism is complex, and a large number of parameters must be extracted from data. Furthermore, the information contained in the data is often limited, and the model may not be fully determined. The solution is to reduce the number of parameters and to estimate them in such a way that they not only describe well the new data but also agree with the existing knowledge. In a previous study, we presented a comprehensive formalism for estimating kinetic parameters subject to a variety of explicit and implicit constraints that define quantitative relationships between parameters and describe specific mechanism properties. Here, we introduce the reader to the QuB software, which implements this constraining formalism. QuB features a powerful visual interface and a high-level scripting language that can be used to formulate kinetic models and constraints of arbitrary complexity, and to efficiently estimate the parameters from a variety of experimental data.

The Drosophila Gr28bD product is a non-specific cation channel that can be used as a novel thermogenetic tool.

Extrinsic control of single neurons and neuronal populations is a powerful approach for understanding how neural circuits function. Adding new thermogenetic tools to existing optogenetic and other forms of intervention will increase the complexity of questions that can be addressed. A good candidate for developing new thermogenetic tools is the Drosophila gustatory receptor family, which has been implicated in high-temperature avoidance behavior. We examined the five members of the Gr28b gene cluster for temperature-dependent properties via three approaches: biophysical characterization in Xenopus oocytes, functional calcium imaging in Drosophila motor neurons, and behavioral assays in adult Drosophila. Our results show that Gr28bD expression in Xenopus oocytes produces a non-specific cationic current that is activated by elevated temperatures. This current is non-inactivating and non-voltage dependent. When expressed in Drosophila motor neurons, Gr28bD can be used to change the firing pattern of individual cells in a temperature-dependent fashion. Finally, we show that pan-neuronal or motor neuron expression of Gr28bD can be used to alter fruit fly behavior with elevated temperatures. Together, these results validate the potential of the Gr28bD gene as a founding member of a new class of thermogenetic tools.