 |
|
|
Mechanisms and regulation of electrolyte transport
in renal tubules.
Our major research interests are investigating
the cellular and molecular mechanisms and regulation of electrolyte
transport in kidney tubules, in particular use of genetically manipulated
animal models, to conduct both in vivo and in vitro microperfusion of
kidney tubules to characterize the functional roles of ion transporters,
pumps and channels in physiology and transport lesions.
My lab, the Small Animal Integrated Renal Function
Core Lab, is an important resource that provides training and services
to support many research projects both inside and outside of Yale University.
The following projects are presently being conducted in our lab:
- To explore the mechanism and regulation of glomerulotubular balance
(GTB), which is an important physiological autoregulation of Na+ Cl-
and HCO3- transport in kidney proximal tubules.
- The study of the physiologic roles of Na+-H+ exchanger isoforms:
by using mice with targeted disruption of NHE genes, we can gain insight
into the molecular mechanisms and regulation of HCO3- transport and
acid-base balance.
- The regulation of Na+ and HCO3- transport by Nitric Oxide (NO)
and Angiotensin II (Figure). Investigations have focused on renal
function in nNOS, iNOS, eNOS and AngII receptor knockout mice.
- The physiological role of K-channels in the regulation of Na+,
Cl- and K+ transport: ongoing experiments using mice with targeted
disruption of the renal K+ - Channel, ROMK (in collaboration with
Dr. Gerhard Giebisch and Dr. Steve Hebert)
- The development of polycystic kidney disease: using mice with mutations
in the proteins PKD1 and PKD2 we are assessing the decline in renal
function as the disease develops (in collaboration with Dr. Peter
Aronson and Dr. Steve Somlo)
- Altered divalent cation handling in Bartter's and Gitelman's syndromes:
Ca2+ and Mg2 transport in ROMK and thiazide-sensitive Na-Cl cotransporter
(TSC) knockout mice (in collaboration with Dr. Steve Hebert and
Dr. Richard Lifton)
- The role of H/K-ATPase in the regulation of K transport: using both
gastric and colonic H/K-ATPase knockout mice, the roles of these isoforms
in the control and potassium-depleted kidney are investigated (in
collaboration with Dr. Michael Caplan)
The major experimental techniques used in this
lab include: Metabolic studies, renal clearance in rats and mice; microperfusion
of the proximal tubule, loop of Henle and distal tubules in vivo; microperfusion
of kidney proximal and collecting tubules in vitro, in rats and mice;
measurement cell pH; and analysis of Na+, Cl-, K+, HCO3- concentrations
in nanoliter samples.
|
Figure caption:
Dose-dependent
biphasic effects of AngiotensinII on fluid (Jv) and bicarbonate
(JHCO3) absorption in kidney proximal tubules. Wang,T.et al. JPET
252 (2): 689-695,1990.
|
Recent publications:
Wang,
T. Inglis, F. M. and Kalb, R. G. Defective
absorption of fluid and bicarbonate in the proximal tubule of mice lacking
neuronal nitric oxide synthase (nNOS). Am. J. Physiol, 279: 518-524,
2000.
Wang, T. Chao-Ling Yang, Thecla Abbiati, Gary E. Shull, Gerhard Giebisch,
and Peter S. Aronson. Essential
Role of NHE3 in Facilitating Formate-dependent NaCl Absorption in the
Proximal Tubule. Am. J. Physiol, 281(2): F288-92, 2001.
Wang, T. Aronson, PS and Giebisch, G. Role
of NHE isoforms in mediating bicarbonate reabsorption along the nephron.
Am. J. Physiol, 2001.
Wang,
T. Peter S. Aronson and Giebisch, G. "The
use of transgenic animals in acid-base transport" Journal of Nephrology
15 (suppl, 5): S151-S160, 2002.
Wang, T. Role
of iNOS and eNOS in modulating proximal tubule bicarbonate transport
and acid-base balance. Am. J. Physiology, 283:F658-F662, 2002.
Lawrence P. Karniski, Tong Wang, Lorraine A. Everett, Eric D. Green,
Gerhard Giebisch, and Peter S. Aronson. Formate-stimulated
NaCl absorption in the proximal tubule is independent of the pendrin
protein. Am J. Physiology, 283: F952-F956, 2002.
Ming Lu, Wang, T., Qingshang Yan, Xinbo Yang, Ke Dong, Mark Knepper,
WenHui Wang, Gerhard Giebisch, Gary Shull and Steven Hebert.
Absence of small-conductance K+ channel (SK) activity in apical membranes
of thick ascending limb and cortical collecting duct in ROMK (Bartter's)
knockout mice. J.B.C. 277: 37881-37887, 2002.
Wang, T. The
effects of potassium channel opener minoxidil on renal electrolyte transport
in the loop of Henle. J Pharmacol Exp Ther, 304 (2): 833-840, 2003.
Zhaopeng Du, William Ferguson and Tong Wang. Role
of PKC and calcium in modulation of the effects of Angiotensin II on
sodium transport in proximal tubule. Am J. Physiology, 284: F688-F692,
2003.
Franz-X. Beck, Wolfgang Neuhofer, Adolf Dorge, Gerhard Giebisch and
Tong Wang. Intracellular
Na+ concentration and Rb uptake in proximal convoluted tubule cells
and abundance of Na+ /K+ -ATPase a1-subunit in NHE3-/- mice. Pflugers
Arch- Eur J Physiol 446:100-105, 2003.
Tong
Wang, Hyacinth Sterling, Wei A. Shao, Qingshang Yan, Matthew A. Bailey,
Gerhard Giebisch and Wenhui Wang. Inhibition
of heme oxygenase decreases sodium and fluid absorption in the loop
of Henle. Am J Physiology,285(3):F484-F-90,2003.
tong.wang@yale.edu
|
 |