University of Virginia Health System

J. Randall Moorman, M.D.
Professor

Our laboratory focuses on molecular electrophysiology. We use the techniques of molecular biology and cellular electrophysiology, including site-directed mutagenesis, microelectrode voltage clamping, patch clamping, and bilayer recording to study the molecular mechanism of ion channel function. Currently, we are focusing on the molecular details of a new kind of ion channel molecule. Phospholemman is a 72-amino-acid membrane protein which is a major substrate for protein kinases in heart and in other tissues; recently, we have shown that it functions as a voltage-dependent chloride channel. We are studying its function using microelectrode voltage clamping of RNA-injected Xenopus oocytes, and electrical recordings of ion currents through single phospholemman channels reconstituted in a synthethic lipid bilayer. In addition to trying to understand what an ion channel looks like and how it works, we are studying its regulation by phosphorylation. We accomplish this by co-expression of several kinds of protein kinases, including the human myotonic dystrophy protein kinase, in oocytes along with the phospholemman channel. We are also actively investigating structure-function relationships of a skeletal muscle sodium channel, and its regulation by phosphorylation. In a separate set of studies, we are investigating dynamical and statistical properties of human heart-rate variability.

Selected Publications:

Kowdley, G.C., Ackerman, S.J., John, J.E., Jones, L.R. and Moorman, J.R. (1994) Hyperpolarization-activated chloride currents in Xenopus oocytes. J. Gen. Physiol.  103:217-230. [View Entrez Listing]

Mounsey, J.P., Xu, P., John, J.E., Gilbert, J., Roses, A.D. and Moorman, J.R. (1995) Modulation of skeletal muscle sodium channels by the human myotonic dystrophy kinase. J. Clin. Invest.  95:2379-2384.

Aghili, A.A., Rizwan-uddin, Griffin, M.P. and Moorman, J.R. (1995) Scaling and ordering of neonatal heart rate variability. Phys. Rev. Lett.  74:1254-1257.

Morrison, B., Moorman, J.R., Kowdley, G.C., Jones, L.R. and Leder, P. (1995) Mat-8, a novel phospholemman-like protein expressed in human breast tumors, induces a chloride conductance in Xenopus oocytes. J. Biol. Chem.  270:2176-2182. [View Entrez Listing]

Kowdley GC, Ackerman SJ, Chen Z, Szabo G, Jones LR, Moorman JR. Anion, cation, and zwitterion-selectivity of phospholemman channel molecules. Biophysical Journal , accepted pending minor revision.

Grant AO, John JE, Starmer CF, Moorman JR. The role of inactivation in open channel block of the sodium channel. Studies with inactivation-deficient mutant channels. Molecular Pharmacology , in press.

Moorman JR, Ackerman SJ, Kowdley GC, Griffin MP, Cala SE, O'Brian JJ, Szabo G, Jones LR. Unitary anion currents through phospholemman channel molecules. Nature , 377: 737-740, 1995.