Voltage-dependent ion channels
My work focuses on voltage-dependent channels, the basis of electrical activity and signalling in neurons and other "excitable" cells. Over 100 voltage-dependent cation channels are now known, with 10 or more expressed in an individual neuron. Each neuron has an "electrical personality" resulting from the complex interplay among those channels. Channel activity is also modulated by cellular signalling mechanisms, on time scales ranging from milliseconds to days. My research addresses three fundamental questions about voltage-dependent ion channels: gating (when is a channel open?), permeation (how do ions interact with the channel pore?), and modulation (how do G proteins and other signalling molecules regulate channel function?). We perform electrophysiological studies on channels either in their native environment (acutely isolated neurons), or on cloned channels in expression systems (e. g., mammalian cell lines). We also use quantitative computer models, as operational descriptions of channel behavior, and as testable hypotheses of the molecular mechanisms underlying channel function. Recent work in the lab has focused on T-type calcium channels, which are involved in generation of rhythmic activity in many cells (e. g., thalamic neurons), and on slow inactivation of voltage-dependent potassium channels. Goals include structure-function studies, and asking how biophysical properties of channels affect the electrical behavior of neurons.
Permeation and gating in T-type calcium channels
Effects of di- and trivalent cations on permeation and gating. Role of T-type channels in entry of trace metals such as Fe2+ and Cd2+ in physiological or pathological conditions.
Slow inactivation of Kv-type potassium channels
Structure-function studies of the mechanism of "U-type" inactivation from closed states. Role of U-type inactivation in electrical excitatability of neurons and pancreatic beta cells.
- Lopin KV, Obejero-Paz CA, Jones SW., Evaluation of a two-site, three-barrier model for permeation in CaV3.1 (α1G) T-type calcium channels: Ca2+, Ba2+, Mg2+, and Na+. J Membr Biol. 2010 Jun;235(2):131-143.
- Obejero-Paz CA, Gray IP, Jones SW. Ni2+ block of CaV3.1 (α1G) T-type calcium channels. J Gen Physiol. 2008 Aug;132(2):239-250.
Permeation and gating in CaV3.1 (alpha1G) T-type calcium channels effects of Ca2+, Ba2+, Mg2+, and Na+.
Khan N, Gray IP, Obejero-Paz CA, Jones SW. J Gen Physiol. 2008 Aug;132(2):223-38.