Physiology and Biophysics Faculty

Research Interests

Cells in almost all tissues are interconnected by gap junction channels. These channels allow the passage of ions and small molecules (< 1kD) from cell to cell thus synchronizing the cells electrically and metabolically. Research in my laboratory is geared towards two goals: 1) Identification of functional domains within the molecular subunits of gap junctions, the connexins. 2) Determination of the physiological function of specific gap junction proteins in tissues.

For identification of functional domains of connexins exogenous expression of wild-type connexins and lab-generated connexin mutants is employed. Functional expression is achieved with the paired oocyte assay and channel function is measured with voltage clamp techniques including patch clamping. Presently the main focus of our studies is to identify pore lining amino acids and to map the position of various channel gates in relation to reference points within the pore.

Recently a second group of gap junction proteins, the pannexins, were discovered. Pannexin expression overlaps with that of connexins, yet connexin specific diseases exist. Thus pannexins must exert a role distinct from connexins. In our laboratory we follow the working hypothesis, that the physiological role of pannexins is to form large nonjunctional membrane channels, which allow the rapid flux of ATP and other molecules across the membrane. ATP release is a key step in the initiation and propagation of calcium waves, a signal pathway in diverse cellular functions including peripheral regulation of blood perfusion. Consistent with such a function, we have observed that pannexin channels are mechanosensitive and highly permeable to ATP. Furthermore, the channels can be activated by extracellular ATP and by cytoplasmic calcium. We also found pannexin expression in erythrocytes, cells that do not form gap junctions but release ATP. This lends additional support to our hypothesis of a non-gap junction function of pannexins.

• Google Scholar Citations
• PubMed Citations

Selected Publications

1. Hu, X. Ma, M. and G. Dahl (2005) Conductance of connexin hemichannels segregates with the first transmembrane segment. Biophysical J., in press.
2. Ma, M. and G. Dahl (2005) Cosegregation of permeability and single channel conductance in chimeric connexins. Biophysical J., in press.
3. Bao L, Locovei S, Dahl G (2004) Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 572(1-3):65-8.
4. Qu Y. and G. Dahl (2004) Accessibility of cx46 hemichannels for uncharged molecules and its modulation by voltage. Biophysical J. 86: 1502-1509.
5. Qu Y, Dahl G. (2002) Function of the voltage gate of gap junction channels: selective exclusion of molecules. Proc Natl Acad Sci USA. 99(2):697-702.
6. Hu, X. and G. Dahl (1999) Exchange of conductance and gating properties between gap junction hemichannels. FEBS Letters 451:113-117.
7. Pfahnl, A. and G. Dahl (1998) Localization of a voltage gate in connexin46 gap junction hemichannels. Biophysical J. 75, 2323-2331.
8. Zhou, X.-W., Pfahnl, A. ,Werner, R., Hudder, A., Llanes, A., Luebke A. and G. Dahl (1997) Identification of a pore lining segment in gap junction hemichannels. Biophysical J. 72, 1946-1953.
9. Dahl, G. R. Werner, E. Levine and C. Rabadan-Diehl ( 1992) Mutational analysis of gap junction formation. Biophysical J. 62, 187-197.
10. Werner, R., E. Levine, C. Rabadan-Diehl and G. Dahl (1989) Formation of hybrid cell-cell channels. PNAS 86, 5380-5384.
11. Dahl G, Miller T, Paul D, Voellmy R, and Werner R. (1987) Expression of functional cell-cell channels from cloned rat liver gap junction complementary DNA. Science 236:1290-1293.
12. Dahl, G., R. Azarnia and R. Werner (l98l) Induction of cell-cell channel formation by mRNA. Nature 289: 683-685.

Curriculum Vitae

• 1974 M.D. Universitat des Saarlandes
• 1974-1978 Wissenschaftlicher Assistant, Physiologisches Institute, Universitat des Saarlandes, Homburg/Saar, West Germany
• 1978-1980 Assistant Professor of Physiology and Biophysics, University of Miami Miller School of Medicine
• 1980-1989 Associate Professor of Physiology and Biophysics, University of Miami Miller School of Medicine
• 1990-present Professor of Physiology and Biophysics, University of Miami Miller School of Medicine