Cellular and molecular mechanisms regulating arterial smooth muscle excitability.
The main goal of my research team is to understand the mechanisms by which local and global calcium signals regulate excitation-contraction coupling and excitation-transcription coupling in arterial smooth muscle cells during physiological and pathological conditions. To tackle these issues, we employ several state-of-the-art techniques including molecular biology, patch-clamp electrophysiology, and confocal and Total Internal Reflections Fluorescence (TIRF) microscopy. We are currently interested in determining the mechanisms by which hyperglycemia induces the activation of a novel calcium signaling modality(persistent calcium sparklets) in arterial smooth muscle, causing increased contraction and consequently, arterial dysfunction during diabetes.
LF Santana, MF Navedo (2009) Molecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle. Journal of Molecular and Cellular Cardiology 47: 436-444.
MF Navedo*, T Takeda, M Nieves-Cintron, JD Molkentin, LF Santana (2010) Elevated calcium sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells. American Journal of Physiology 298: C211-C220. *corresponding author. This article is accompanied by an editorial from Dr. Mark T. Nelson highlighting the novel aspects of the study.
MF Navedo, EP Cheng, C Yuan, VS Votaw, JD Scott, LF Santana (2010) Increased coupled gating of L-type calcium channels during hypertension and Timothy syndrome. Circulation Research 106: 748-756. This article is accompanied by an editorial from Dr. Don Bers highlighting the novel aspects of the study.
LF Santana, MF Navedo (2010) Natural inequalities: why some L-type Ca2+ channels work harder than others. Journal of General Physiology 136: 143-147. Featured on the cover of the Journal.
EP Cheng, C Yuan, MF Navedo, RE Dixon, M Nieves-Cintrón, JD Scott, LF Santana. (2011) Restoration of normal L-type Ca2+ channel function during timothy syndrome by ablation of an anchoring protein. Circulation Research 109: 255-261.
Takeda, MA Nystoriak, M Nieves-Cintrón, LF Santana, MF Navedo* (2011) Relationship between calcium sparklets and sarcoplasmic reticulum calcium load and release in rat cerebral arterial smooth muscle. American Journal of Physiology - Heart 301: H2285-2294. *corresponding author.
RE Dixon, C Yuan, EP Cheng, MF Navedo, and LF Santana (2012) Calcium signaling amplification by oligomerization of L-type Cav1.2 channels. Proceedings of the National Academy of Science 109: 1749-1754.