Infant death and uterine insufficiency - New therapies within range

Innsbruck (FWF) – Animal experiments have shown that SK3 channels, which can be found in certain nerve and muscle cells, are important for the maintenance of respiration and the regulation of uterine contractions. In the course of an international project sponsored by the Austrian Science Fund (FWF), Hans-Günther Knaus from the Institute of Biochemical Pharmacology at the University of Innsbruck has found a pharmacological method to activate or switch off the channels, as required. New treatments for respiratory disorders, sudden infant death and uterine insufficiency seem to be within reach.

The breeding of genetically altered mice (Science 289, 1942-1946 (2000)) stood at the beginning of Hans-Günther Knaus' research activity in co-operation with the Vollum Institute in Portland, Oregon, and the Max-Planck-Institute in Heidelberg, Germany. The density of the SK3 channels in the test animals was increased by a factor of five to prove a connection between an increased activity of SK3 channels and respiratory disorders. Knaus: "The genetically altered animals were not able to increase their breathing frequency in the case of a drop in O2 in the ambient air. They died from respiratory arrest at oxygen concentrations that were absolutely safe for their siblings, which had not been genetically altered." Once the excessive activity of the channels had been reduced, the breathing frequency of the test animals was comparable to that of their siblings. The genetically altered animals additionally showed a significantly extended parturition process, which in most cases ended lethal both for the mother and the offspring. "Switching off" the SK3 channels by pharmacological treatment ten days before parturition eliminated the problem.

The results of Knaus' research work lead to the conclusion that increased activity of the SK3 channels is closely related to the sleep apnoea syndrome and sudden infant death. Both syndromes involve the cessation of breathing during sleep. Pharmacological regulation of SK3 channels could eliminate this possibly lethal risk. A research project exclusively dedicated to the development of SK-channel-specific drugs is currently in preparation.

Ao. Univ.-Prof. Hans-Günther Knaus
Institute of Biochemical Pharmacology
University of Innsbruck
P + 43 512 507 3156