Email:  cbevense@uab.edu
  Telephone: 205.934.1785
  Fax: 205.975.7679
  Bldg/Room: MCLM 868

Research

Regulation of ion channels and transporters

Work in the laboratory is focused on ion channels and transporters involved in health and disease. Using a variety of electrophysiological techniques as well as cellular and molecular approaches we examine ion movement across the cell membrane. In one study we have examined the potential role of stretch-activated ion channels (SACs) in the development of heart failure. Using a model of volume overload-induced heart failure, we have demonstrated a basally active, Gd³⁺ and GSMTx-4-sensitive SAC that is transiently elevated in left ventricular myocytes in early stages of the disease process. Characterizing the function of SACs during the progression of heart failure will provide the foundation for identifying the channels at the molecular level and developing novel therapeutic compounds. Studies are also underway to examine how Na/bicarbonate cotransporters (NBCs) are regulated. NBCs are expressed in many tissues including kidney, heart and brain and are important in the regulation of intracellular pH and bicarbonate reabsorption in the kidney. We use the macropatch technique which allows us to gain access to the cytosolic surface of the cell membrane and assess the effects of regulators such as phosphoinositides, phosphatases and kinases on NBC function. An additional area of interest is examining the role of potassium channels in the kidney. ROMK is one example of a channel the laboratory is interested in. ROMK is an inwardly rectifying K⁺ channel cloned from the distal nephron of the kidney, where it is vital for potassium homeostasis. Studies will examine factors that can modulate ROMK channel activity which ultimately affect K⁺ handling by the kidney.

Selected Publications

• McNicholas, C.M., Guggino, W.B., Schwiebert, E.M., Hebert, S.C., Giebisch, G., and Egan, M.E.  Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound, glibenclamide, is enhanced by co-expression with the ATP-binding cassette transporter CFTR.  Proc Natl Acad Sci USA, 93, 8083-8088, 1996.

• McNicholas, C.M., Nason, Jr. M.W., Guggino W.B., Schwiebert, E.M., Hebert, S.C., Giebisch, G. & Egan, M.E.  A functional CFTR-NBF1 is required for ROMK2-CFTR interaction.  Am J Physiol, 273, F843-F848, 1997.

• Peter, K., Varga, K., Bebok, Z., McNicholas-Bevensee, C.M., Schwiebert, L., Sorscher, E.J., Schwiebert, E.M. & Collawn, J.F. Ablation of internalization signals in the carboxyl-terminal tail of the cystic fibrosis transmembrane conductance regulator enhances cell surface expression. J Biol Chem, 277 (51), 49952-49957, 2002.

• Hardiman, K.M., McNicholas-Bevensee, C.M. Fortenberry, J., Miles, C.T., Malik, B., Eaton, D.C. & Matalon, S. Regulation of amiloride-sensitive lung Na⁺ transport by basal nitric oxide. Am J Resp Cell Mol Biol, 30 (5) , 720-8, 2004

• Hickman-Davis, J.M., McNicholas-Bevensee, C.M., Davis, I.C., Ma, H.P. Davis, G.C., Bosworth, C.A. & Matalon, S. Reactive species mediate inhibition of alveolar type II sodium transport during mycoplasma infection. Am J Respir Crit Care Med, 173, 334-344, 2006.

• McAlear, S.D., Liu, X, Williams, J.B., McNicholas-Bevensee, C.M, and Bevensee, M.O. Electrogenic Na/HCO₃ Cotransporter (NBCe1) Variants Expressed in Xenopus Oocytes: Functional Comparison and Roles of the Amino and Carboxy Termini. J Gen Physiol, 127, 639-658, 2006.

• McNicholas-Bevensee, C.M., DeAndrade, K.B., Bradley, W.E., Dell'Italia, L.J., Lucchesi, P.A. and Bevensee, M.O. Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure. Cardiovasc Res 72, 262-270, 2006.