The patch clamp principle

The principle of the method is very easy – as are many ingenious innovations. A glass pipette with a tip diameter of only one thousandth millimeter is pressed gently on the cell membrane. Vacuum leads to a gigaseal between pipette wall and membrane (“on cell” configuration), so that the ion channels below the opening of the pipette tip are the only connection between the inner side of the cell and the electrode fluid in the pipette. When suction is applied to the pipette or a short-time voltage-clamp is applied, the membrane breaks and the cytoplasm and the pipette solution start to mix (“whole cell” configuration). Withdrawing the pipette will excise a patch (“excised patch” configuration), which can then be analyzed.

This biophysical method made it possible to exactly determine when a single ion channel opened or closed. In combination with biochemical and molecular biological methods, the molecular composition of ion channels, the changes in configuration upon opening and closing and their specificity towards certain ions and chemical transmitter substances can be analyzed. Today, thousands of laboratories use the patch clamp method in order to examine ion channels in animal and plant tissues and cells. Life processes such as the fertilization of an egg cell, the uptake of nutrients by plant cells, insulin release by the pancreas, heart muscle contraction and the signal transfer in neurons depend on ion channels.

Already at the beginning of his career in the research laboratory of Bernard Katz, Sakmann was interested in the function of the central nervous system. Together with Tomoyuki Takahashi, Sakmann developed a method to expose neurons in brain slices, so that patch clamp techniques could be applied to measure synaptic currents. In order to investigate the elementary processes of synaptic signal transmission in close cooperation with molecular biologists, Sakmann moved his laboratory from Göttingen, where he had been collaborating with Erwin Neher for sixteen years, to Heidelberg, one of the best molecular biology centers in Germany. In Heidelberg, Sakmann founded the Department of Cell Physiology at the Max Planck Institute for Medical Research in 1989.

The Nobel Prize

Two years later Sakmann was awarded the Nobel Prize of Physiology or Medicine together with Neher. When Sakmann joined the Max Planck Institute in Heidelberg, the institute began to reorient itself and focus on the molecular and cellular basis of life. This research was further strengthened when molecular and neurobiologist Peter Seeburg joined the institute in 1996. The cooperation of the two research groups on the clarification of the physiological and pathological functions of the synapses of the central nervous system on the molecular level using biophysical and molecular biological methods turned the listed red brick building into a leading international center of molecular neurobiology.

Numerous diseases are caused or influenced by the failure or defective functions of ion channels (channelopathies). Channelopathies include familial hemiplegic migraine and episodic ataxia, a form of involuntary muscular movement. This disease is caused by a mutation of the alpha(1a) calcium channel gene on chromosome 19p13. Ion channels are also involved in myocardial arrhythmia, diabetes, high blood pressure, incontinence, multiple sclerosis, diabetes, angina pectoris and epileptic seizures.