The Molecular physiology and channelopaties research group from the CEXS-UPF is formed by several PhD students, postdocs, a technician and a couple of principal researchers with teaching duties. Miguel Angel Valverde leads the group since 1999, when he came to Barcelona from King’s College in London.
The aim of the group is two-fold. On the one hand, they try to understand how the ionic channels are activated, how they sense the physical or chemical signals that tell them to open or close. The second goal is to understand what happens when these channels don’t work correctly.
Ca2+ and its role in disease
Different types of ion channels are present in all cells, but they all have a unique, essential function: to modify the electric potential of the cell with the ultimate goal of regulating the intracellular Ca2+ concentration. Indeed, Ca2+ is not only an ion itself, but also a signalling molecule involved in many processes, such as muscle contraction, neurotransmitter release, or even gene transcription. This is why, when its concentration is deregulated, problems as diverse, common and complex as cardiovascular, respiratory or neuronal pathologies can arise. And these are precisely the channelopaties that the group studies.
Hypertension is one of the most important predictors of cardiovascular diseases. And one of the causes of hypertension is the contraction of the arteries, which makes their diameter smaller. This contraction is started by the Ca2+ signalling in the vascular smooth muscle. Ca2+ concentrations are also crucial for the immune system response, which explains why the group is interested in asthma, an inflammatory pathology. Finally, migraine is caused by a hyper excitability of the brain cortex, which in its turn is caused by an increase in the activation of synaptic transmission. Again, we find the usual suspect, an increase in Ca2+ levels, at the beginning of the chain of events that lead to migraine.
A multidisciplinary approach
role of ion channels in these channelopaties is studied at the genetic, molecular, cellular and physiological level. The group collects population samples, either by themselves or in collaboration with clinical or epidemiological groups. They sequence some candidate genes to find any genetic variations (called polymorphisms) that may be linked to the pathology. Once there is a polymorphism that represents a clear risk or beneficial factor, the group studies why this change in the genome is associated with the disease. “We don’t just link a gene to a disease. Instead we want to understand the whole process: how this gene affects the protein structure, and how that change in structure affects the function of the channel and the Ca2+ concentration”, explains Valverde.
They introduce the genetic changes under study in cells in culture and they analyse how the Ca2+ concentration varies by fluorescent microscopy, or do electrophysiology studies to look at the electrical activity of a single channel.
Such a multidisciplinary work requires lots of collaborations, and the laboratory has found many of them within the PRBB. They have worked with researchers at the IMIM and with neurologists and pediatricians at the Hospital del Mar for the cardiovascular and asthma studies; with groups at the CRG and other colleagues at the UPF and the GRIB for some genetic, biochemical and computer modelling aspects of the studies. “We do truly translational research, and are compulsive collaborators”, concludes Valverde with a smile.
This article was published in the El·lipse publication of the PRBB.