The recording of action potential currents as an assessment for drug actions on excitable cells.
The use of the cell-attached patch clamp configuration to record action potential currents is shown to have utility in the testing for drug actions on ion channels in excitable cell membrane. A patch pipette was used to isolate a small patch of cell membrane on cultured hippocampal or hypothalamic neurons and spontaneous R-C coupled action potential currents, with well-defined Na+ and K+ components, were recorded. The addition of several potassium channel-blocking drugs to the bath solution completely abolished the after-hyperpolarization phase of the action potential currents while preserving the sodium spike. These drugs have previously been shown to block a calcium-dependent potassium channel in cultured hippocampal neurons, a channel that is responsible for the late slow after-hyperpolarization macroscopic current recorded in these cells. The addition of tetrodotoxin to the bath solution eliminated the R-C coupled currents. The novel approach of using the recording of action potential currents to assess drug actions on ion channels would be expected to be applicable to a variety of excitable cells.
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
J G
JG
McLarnon
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; D010627:Phenethylamines; D015221:Potassium Channels; D013449:Sulfonamides; C059921:tedisamil; C063533:dofetilide