Health Sciences Center
Hospital and Clinic
Primate Center
Public Health
Tropical Medicine

Associate Professor of Medicine
Ph.D.: American University of Beirut

My research is focused on studying the cellular and molecular characteristics of epithelial ion transport and regulation of intracellular pH particularly those relevant to renal epithelia. These studies involve using basic molecular biology techniques to express transporters and/or channels in frog oocytes and other mammalian cells in order to study the properties of these transport mechanisms. The methods in use include ion-selective microelectrodes, two-electrode voltage clamp, optical measurements of intracellular pH by fluorescence and the isolated perfused kidney tubule preparation. Several projects are underway.

The first study aimed at investigating CO2 transport, generally thought to cross membranes by solubility diffusion, and the possibility that it could be transported through water channels known as AQPs. This work, demonstrating that AQP1 was permeable to CO2, was the first evidence that a gas such as CO2 could be transported through a channel. As a continuation of this work, we are investigating the role of carbonic anhydrase in mediating CO2 transport. We have characterized the role of two isozymes, CA-II and CA-IV and we are currently investigating the interaction of CA-II and CA-IV with expressed HCO3- transporters including the anion exchanger AE1 and the Na+/(HCO3-)n co-transporter NBC.

Extending the CO2 studies to NH3, we have recently demonstrated that the membrane permeability of NH3 was greatly enhanced when AQP1 was expressed. This study may be particularly important since transport through a channel suggests that regulation of NH3 transport may be feasible. These studies are being pursued further to investigate the role of other AQP(s), namely AQP2, AQP3 and AQP4, all of which are present in the collecting duct, in mediating NH3 transport.

Another study in my lab that stemmed out from the NH3/NH4+ studies was regulation of Na+ transport through the epithelial Na+ channel, ENaC, by NH4+. In this study, we demonstrated that external NH4+ inhibited Na+ transport through ENaC in a manner independent from an intracellular pH effect. This may be very significant in the collecting duct during acid/base disturbances such as systemic metabolic acidosis when NH4+ levels are greatly elevated. We are currently expanding these studies to further investigate the mechanism of NH4+ inhibition of ENaC and the role of pH.

Other works in progress include molecular and functional characterization of novel NH4+ transporters previously unidentified in the kidney. We have succeeded in isolating two clones from the kidney cortex, originally cloned from yeast. We are in the process of expressing them in oocytes and mammalian cells in order to study their transport properties. These transporters are the first to act as (potential) specific NH4+ transporters and have never been characterized before.

Other studies include determining whether a mutation in the Na+/(HCO3-)n co-transporter (NBC) is responsible for a form of proximal tubular acidosis (PTA) in a pool of patients from Costa Rica. This work is potentially very important, because a mutation resulting in a loss of function of Na+/(HCO3-)n that could cause PTA is new and not well known as a cause of this disease.

Recent Publications:

A PubMed listing of research publications for Nazih L. Nakoul, Ph.D.

Contact: