 |
|
 |
Perspectives
Gerhard
Giebisch
Why did
I become interested in the kidney? I have always been influenced and
greatly affected by books, and I read a great deal when I was a medical
student. I distinctly remember the lasting effects of a book that one
of my clinical professors in Internal Medicine allowed me to read. It
was Homer Smith's "Lectures on the Kidney", a collection of his Porter
Lectures in which he described in a very lucid manner the application
of renal clearance methods to the study of water and electrolyte metabolism.
I think it was this book that made me want to know more about the mechanisms
by which electrolytes were regulated, how single renal tubule cells
sense the lack or an excess of a specific electrolyte and what cell
transport processes were involved in excreting or retaining just the
right amounts of fluid and salts to prevent distortions of the volume
and composition of body fluids. At that time I was working in hospital
wards largely filled with patients suffering from severe and relentlessly
progressing renal or liver diseases, and the consequences of deranged
water and electrolyte balance were very striking and painfully impressive.
Although my future work would be almost entirely confined to addressing
physiological problems, I have remained interested in pathophysiology
and the application of physiological principles to the disturbances
of electrolyte transport to disease states.
When I
started my research career, renal physiology was in the process of transition,
from clearance approaches in the whole animal to studies at the single
nephron level, followed by impalement of single tubule cells to unravel
the driving forces responsible for transport of ions across defined
single membranes of tubule cells. Our work now focuses on learning more
about the polar organization of ion pumps and ion channels in kidney
tubules. An interesting new development is the generation of animal
models in which individual transporters are genetically altered, i.e.
lacking or overexpressed. By studying transport in "knock-out"
animals, we can obtain knowledge not only of the function of individual
transporters, but also about compensatory mechanisms that attenuate
the activation of functional lesions. By applying a wide variety of
techniques, we explore the basic mechanisms of electrolyte transport,
especially those of sodium, potassium, chloride and hydrogen ions, and
attempt to integrate such knowledge with studies on overall organ function.
Our aim is to integrate knowledge obtained by studying single transport
molecules into the larger integrative transport functions of renal epithelia.
This approach is complemented and strengthened by the activities in
other laboratories of the department in which a variety of electrophysiological
and other molecular biological techniques are used to study transport
phenomena in cell signalling.
|
 |