Section of Cardiology

• George A. Porter, Jr., MD, PhD, Associate Research Scientist
  Special Interests: cell signaling, cardiac development, congenital heart disease, imaging techniques of embryos

Non-Faculty members (technical, clerical)

• Ryan MakuckResearch Assistant

Current Grant Support

Name	Title	Funding Agency	Dates
George A. Porter, Jr., MD, PhD	Mechanisms of calcium signaling in the early heart	NIH/YCHRC (P30, HD27757)	12/1/2000-11/30/2003
George A. Porter, Jr., MD, PhD	Calcium-mediated modulation of cardiac development	NIH (1 K08 HL70765)	7/1/2002-6/30/2007

Publications for 2001 and 2002:
Original reports:
1. Porter GA, Rivkees SA. The ontogeny of humoral heart rate regulation in the embryonic mouse. Amer J.Physiol. 281:R401-407, 2001.

2. Moltedo JM, Snyder CS, Porter GA, State MW. Sinus node dysfunction associated with lithium therapy in a pediatric patient. Tex Heart Inst. J. 29, 2002.

3. Porter GA, Makuck RF, Rivkees SA. Reduction in intracellular calcium levels inhibit myoblast differentiation. J Biol Chem., 277: 28942-7, 2002.

4. Rentschler S, Levine R, Zander J, Porter G, Rivkees SA, Fishman, GI. Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U S A. 99: 10464-10469, 2002.

5. Moltedo JM, Kopf G, Mello D, Porter GA. Right coronary artery arising from the left ventricular outflow trace. A rare congenital anomalies of the coronary arteries. Pediatr Cardiol. In press.

6. Porter GA, Makucki RF, Rivkees SA. Intracellular calcium plays an essential role in cardiac development. Developmental Dynamics (in press).

Reviews and Chapters:
1. Rivkees SA, Zhao Z, Porter GA, Turner C. Influences of adenosine in the fetus and newborn. Mol Genetics Metabol, 74:160-171, 2001.

Research Interests and Activity
I am interested in the signals that regulate myocyte differentiation (the formation of cardiac muscle cells from undifferentiated precursors) and cardiac morphogenesis (the formation of the definitive heart structure). In particular, I study the role of intracellular calcium signals in these processes. These studies have focused on: 1. The source of intracellular calcium in immature cardiac myocytes, 2. The cell membrane receptors that modulate calcium signals, 3. The cytoplasmic messengers that mediate the action of calcium signals, 4. The regulation of gene expression by calcium signaling, and 5. The morphologic alterations induced by abnormal calcium signals in the early heart.

These studies are performed using standard molecular and cell biological techniques. I use confocal and epifluorescence imaging of both live and fixed specimens. I also routinely use cell culture and whole embryo culture to study the effects of various agents on early cardiac physiology and development. Finally, I use confocal calcium imaging techniques to study the mechanisms by which intracellular calcium levels are regulated.

Recent experiments in my laboratory have demonstrated that decreasing intracellular calcium levels inhibits myocyte differentiation and alters the formation of the cardiac ventricles. In particular, decreasing calcium levels with calcium channel blockers yields embryonic hearts that loop abnormally and lack a right ventricle. These treatments also selectively inhibit the expression of transcription factors (GATA4) and cytoskeletal proteins (myosin light chain 2V) in the developing ventricles.

Ongoing experiments are aimed at further defining the pathways by which calcium levels are regulated and by which these signals control gene transcription and cardiac development using the techniques described above.