In the new study, Yu, Kim and their colleagues looked for VNO potassium channels, which admit positively charged potassium ions. They began by setting up whole-cell patch clamp tests, in which tiny electrodes measure the net flow of charged ions through the membranes of neurons in a slice of mouse VNO tissue. To determine the contribution of potassium ions to these currents, they replaced the potassium ions in the neurons with chemically similar cesium ions, which cannot get through potassium channels. When these potassium-depleted VNO neurons were exposed to pheromone-containing mouse urine, the usual net inward flow of positive charge was significantly greater than it had been when the neurons contained potassium.
That and other experiments with the VNO tissue slices suggested that potassium ions normally flow out of VNO neurons through potassium channels when a VNO receptor is activated. This was not completely unexpected; neurons typically have a greater concentration of potassium ions inside than outside, leading to an outward flow when potassium channels are opened. The outward flow originates mostly from the main bodies of neurons and helps reset neurons to a resting state voltage. However, in the VNO neurons a strong outward flow of potassium also occurred within the dendrites, directly countering the inward flow of positive ions that would activate the neurons. "It seemed a bit bizarre that such an important system would work against itself in this way," Yu says.
The team was able to zero in on the two potassium channels responsible, which are known as SK3 and GIRK. But when they set up experiments to evaluate these channels not in VNO tissue slic
|Contact: Gina Kirchweger|
Stowers Institute for Medical Research