Ion channels are the molecular units of electrical signaling in cells. They are proteins that regulate the movement of ions—such as sodium, calcium, and potassium—into and out of cells. They are responsible for the conversion of external sensory signals to the electrical language of the nervous system and for the integration of these signals to generate appropriate behavior. Ion channels are also important for the generation and regulation of the heartbeat, for contraction of muscles, and for the release of hormones in the bloodstream. The body contains a large variety of ion channel types, specialized to select for certain species of ions and to selectively open and close in response to a number of different stimuli, such as the binding of a neurotransmitter molecule or a change in the voltage that exists across a cell's membrane. Work in the Aldrich laboratory is directed towards understanding the mechanisms of ion channel function and the role of ion channels in electrical signaling and physiology. This research relates to transduction, processing, and transmission of information in the nervous and other physiological systems and to basic mechanisms of coupled conformational changes in signaling proteins. We use a combination of molecular biology, electrophysiology, biophysics, cellular and systems physiology, and computational biology.
Recently we have focused on the mechanisms of gating and the physiological roles of voltage- and calcium-activated (BK) potassium channels. These ion channels proteins are important in excitable and nonexcitable cells of a very wide range of physiological systems. BK channels are also an outstanding model system for the study of regulated conformational changes in proteins due to their dual activation (by membrane voltage and by calcium binding) and their particular suitability for high-resolution functional manipulation and measurements, including high quality single molecule studies. The broad role of these channels in several tissues provides a rich environment for studying their involvement in cellular and systemic physiological mechanisms. Our work on these channels has been a combination of biophysical studies directed towards understanding the mechanisms of channel gating and transgenic and physiological studies directed towards understanding their role in physiological systems.