Covarrubias Research

Barber A.F., Carnevale V., Klein M.L., Eckenhoff R.G., Covarrubias M. (2014). Modulation of voltage-gated Na⁺ channels by sevoflurane involves multiple sites and distinct mechanisms. Proc. Natl. Acad. Sci. 111(18):6726-6731.

This study combined electrophysiology and molecular dynamics simulations to elucidate the mechanism underlying the inhibition of a voltage-gated sodium channel by the general anesthetic sevoflurane. 

Ritter, D.M., Zemel, B., Hala, T., O’Leary, M., Lepore, A. and Covarrubias, M. (2015). Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury. J. Neurosci. 35:972-984.

We discovered that the hyperexcitability responsible for spinal cord injury-induced neuropathic pain can result from dysregulated trafficking of the Kv3.4 potassium channel to the membrane of putative dorsal root ganglion nociceptors. This study combines analysis of spinal cord injury-induced pain behaviors, electrophysiology, molecular biology and confocal imaging.

Covarrubias, M., Barber A.F., Carnevale, E., Treptow, W. and Eckenhoff, R.G. (2015). Mechanistic insights into the modulation of voltage-gated ion channels by inhalational anesthetics. Biophys. J. 109:2003-11.

This review article discusses the molecular mechanisms underlying the modulation of voltage-gated ion channels by general anesthetics. It mainly focuses on the work from our lab and discusses a perspective of implications and new directions. 

Fineberg, J.D., Szanto, T.J., Panyi, G. and Covarrubias, M. (2016). Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by quaternary ammonium ions. Sci. Rep. (Nature) 6:31131.

This article represents a culmination of a series of studies that have investigated a novel mechanism of potassium channel inactivation involving failed coupling between the voltage sensor and an internal activation gate in the pore domain. This mechanism does not require opening of the pore and might be critical for the regulation of subthreshold depolarizations and backpropagating action potentials in the nervous system.

Zemel, B.M., Muqeem, T., Brown, E.V., Goulão, M., Urban, M.W., Tymanskyj, S.R., Lepore, A.C. and Covarrubias, M. (2017). Calcineurin Dysregulation underlies spinal cord injury-induced K⁺ channel dysfunction in DRG neurons. J. Neurosci. 37:8256-8272.

In this study, we discovered that spinal cord injury (SCI)-induced upregulation of the Regulator of Calcineurin 1 (RCAN1) attenuates the Kv3.4 current in DRG neurons through inhibition of calcineurin (CaN). Thus, dysregulation of the RCAN1/CaN/Kv3.4 pathway is a factor contributing to DRG hyperexcitability associated with persistent pain induced by SCI.