My research is oriented towards an understanding of the mechanisms that regulate the electrical properties of excitable and non excitable muscle cells from the cardiovascular system. This involves the study of two distinct cell types: cardiac myocytes, and arterial smooth muscle myocytes. Both muscle cell types are equipped with an exquisite ion channel machinery that govern the contraction-relaxation cycles to ensure an efficient blood supply to the whole body. Although, cardiac cells and smooth muscle cells are different in several major aspects, as muscle cells, they share many common features as well. These features involve the intracellular calcium dynamics, and several of the ion channels present in both cell types. My research studies are focused in the study of ion channels addressing their functional as well as their biochemical aspects. For this purpose I use several techniques ranging from ion channel reconstitution and patch clamp, to ion channel immunodetection with different procedures such as, immunoprecipitation, western blotting and confocal microscopy.

I am also interested in the use of pharmacological compounds that modulate the activity of ion channels as potential tools to develop therapeutical agents. The projects in my lab include the study of pharmacological regulation of ionic channels in the heart and also in arterial smooth muscle, using voltage clamp techniques in isolated myocytes. A major portion of my research efforts is dedicated to study the role of KCa channels in arterial smooth muscle cells. KCa channels are activated by both voltage and calcium and have been proposed as a fundamental part of a novel negative feedback mechanism in arterial smooth muscle. This mechanism includes the activation of the KCa channels by local Ca2+ release events or Ca2+ sparks. As most ion channels in the body, KCa channel are composed by different subunits; a main pore forming a subunit and regulatory b subunits. In arteries, an increasing amount of evidence suggests a key role for the smooth muscle specific subtype b1 subunit. Experimental models have demonstrated that lack of the b1 subunit lead to an impaired response of the KCa channels.

This dysfunction contributes to elevated arterial tone leading to the development of elevated blood pressure and an enlarged heart (Brenner et al, Nature 407: 870-876, 2000). Thus, studies of arterial KCa channels and its molecular properties shed light on the ionic mechanisms that contribute to high blood pressure or hypertension. Hypertension is the most common form of cardiovascular disease, affecting approximately one in four Americans. Although potentially life-threatening, hypertension is one of the most preventable and treatable types of cardiovascular disease. High blood pressure can cause many other types of cardiovascular disease, including stroke and heart failure.

Robert Brenner, Guillermo J. Perez, Adrian D. Bonev, Delrae M. Eckman, Jon C. Kosek, Steven W. Wiler, Andrew J. Patterson, Mark T. Nelson, and Richard W. Aldrich. Vasoregulation by the beta1 subunit of the calcium-activated potassium (BK) channel. (2000) Nature 407: 870-876. PubMed ID: 11057658

Pérez G. J., A. D. Bonev, and M.T. Nelson. Micromolar calcium from sparks activates calcium-sensitive potassium channels in cerebral artery smooth muscle. (2001) Am J Physiol 281(6): C1769-75. PubMed ID: 11698234

Wellman GC, Nathan DJ, Saundry CM, Perez G, Bonev AD, Penar PL, Tranmer BI, Nelson MT. Ca2+ sparks and their function in human cerebral arteries. (2002) Stroke. 33(3):802-8. PubMed ID: 11872907

M.J. Pozo, G. J. Pérez, M. T. Nelson, and G. M. Mawe. Ca(2+) sparks and BK currents in gallbladder myocytes: role in CCK-induced response. (2002) Am J Physiol Gastrointest Liver Physiol 282(1): G165-74. PubMed ID: 11751170

Di Diego JM, Cordeiro JM, Goodrow RJ, Fish JM, Zygmunt AC, Pérez GJ, Scornik FS, Antzelevitch C. Ionic and cellular basis for the predominance of the Brugada Syndrome phenotype in males. (2002) Circulation 106: 2004-2011 PubMed ID: 12370227

Antzelevitch C, Zygmunt AC, Fish J, Perez G, Scornik C. How Do We Measure Repolarization Inside the Heart? In: Cardiac Repolarization. Bridging Basic and Clinical Science, Gussak I and Antzelevitch C, editors. (2003) Humana Press, NY, pp. 91-110,.

Charles Antzelevitch, PhD, Luiz Belardinelli, MD, Lin Wu, MD, Heather Fraser, PhD, Andrew C. Zygmunt, PhD, Alexander Burashnikov, PhD, José M. Di Diego, MD, Jeffrey M. Fish, DVM, Jonathan M. Cordeiro, PhD, Robert J. Goodrow, Jr, Fabiana Scornik, PhD, and Guillermo Perez, PhD. Electrophysiologic Properties and Antiarrhythmic Actions of a Novel Antianginal Agent. (2004) J Cardiovasc Pharmacol Ther. Suppl 1:S65-83. PubMed ID: 15378132

Pérez G. Twinkle Twinkle Little Spark: Out of Tune Potassium Channels. (2005) In: Pumps, Transporters, and Ion Channels. Sepu?leveda and Bezanilla, Ed. Kluwer Academic/Plenum Publishers, New York NY, 15: 145-155,.

Pérez, Guillermo J. Tamoxifen dual effect on arterial KCa channels does not depend on the presence of its beta1 subunit (2005) Journal of Biological Chemistry 280(23): 21739-21747. PubMed ID: 15826942

Fabiana S. Scornik, Ph.D., Mayurika Desai, M.S., Ramón Brugada M.D., Alejandra Guerchicoff, Ph.D. , Guido D. Pollevick, Ph.D., Charles Antzelevitch, Ph.D., and Guillermo J. Pérez Ph.D. Functional expression of the "cardiac type" Nav1.5 sodium channel in canine intracardiac ganglia. (2006). Hearth Rhythym (3)7: 842-850. PubMed ID: 16818219