Joao Carvalho-de-Souza, D.V.M., Ph.D.

I am interested in ion channels and membrane biophysics. Specifically, my research focuses on noncanonical mechanisms of coupling in voltage-gated ion channels. This type of coupling between the voltage sensor domains (VSDs) of a channel and its ion-conducting pore domain (PD) is structurally and functionally complex, and new discoveries, including those made by my previous work (see links below), are adding to the current knowledge about ion channels in general.

Noncanonical coupling between a VSD and the PD of a channel may be a universal mechanism present in all voltage-gated ion channels. The physical coupling between a VSD and a PD in a channel is part of the voltage dependence process and mechanisms of an ion channel, namely activation and inactivation of all kinds. Noncanonical coupling may also be involved in genetic diseases of ion channels, generally called channelopathies.

Of special interest in my research is the notion that the noncanonical coupling is a key process in those heteromeric voltage-gated K+ channels formed by different Kv subunits. These channels are interestingly involved in diseases such as epilepsy, sick-sinus syndrome, cone dystrophy, chronic pain, addition, and more. 

In my lab, I study these heteromeric Kv channels when expressed in primary cells (neurons and myocytes), in tissues (brain slices or muscle strips), or in heterologous systems such as HEK cells or Xenopus oocytes. With the heterologous systems, we have the chance to test mutations in the plasmid cDNA for the proteins that form the channels. These mutations can be disease-causing mutations or simply designed to answer a scientific question.

The methodologies we use to answer our scientific questions include site-directed mutagenesis, in vitro transcription, cell/oocyte culture, patch clamp electrophysiology, voltage-clamp fluorometry, optocapacitance, and more.

Bibliography

https://pubmed.ncbi.nlm.nih.gov/?term=carvalho-de-souza+jl&page=3&sort=date

https://scholar.google.com/citations?user=q2tVYQMAAAAJ&hl=en