The cells of the renal proximal tubule can accomodate substantial variations in tubular sodium load without significant changes in intracellular composition. The coupling of sodium (Na) to potassium (K) transport via the basolateral Na-K ATPase requires regulation of basolateral potassium conductance to maintain intracellular K homeostasis during marked changes in net Na transport. Any defect in this regulatory process could lead to serious electrolyte imbalance at both the intracellular and extracellular level, since the kidney is responsible for regulation of plasma electrolytes. The proposed research addresses the mechanism of this link between net Na transport and basolateral K conductance using the techniqes of isolated perfused tubules and patch-clamped cell membraes. The former method would provide information about regulation of whole membrane GK, whereas the latter technique would elucidate the basolateral potassium pathway at the single channel level. Since the P.I. has already identified two types of K selective channel at the basolateral membrane of this preparation, the present proposal would examine both the relative contribution of each channel type to the membrane GK and the role of cytoplasmic and extracellular factors in the regulation of channel activity and conductance. The following possible regulators of basolateral potassium conductance will be specifically examined in both intact tubules and membrane patches: (1) cytosolic and extracellular K, (2) cytosolic calcium (3) pH, (4) the cytosolic ATP/ADP ratio, (5) cell membrane potential, (6) membrane deformation, (7) cell volume. The use of amphibian proximal tubules with their larger cell size and lower metabolic rates would simplify many of the experimental procedures while still providing a description of the K regulatory process common to both amphibian and mammalian proximal tubules. Finally, the results of these studies would presumably be applicable not only to the proximal tubule but to many other sodium transporting epithelia as well.
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| Sackin, H (1995) Mechanosensitive channels. Annu Rev Physiol 57:333-53 |
| Sackin, H (1995) Stretch-activated ion channels. Kidney Int 48:1134-47 |
| Cemerikic, D; Sackin, H (1993) Substrate activation of mechanosensitive, whole cell currents in renal proximal tubule. Am J Physiol 264:F697-714 |
