Permeation and block of dopamine-modulated potassium channels on rat striatal neurons by cesium and barium ions.
1. In cell-attached patch-clamp recordings from freshly dissociated rat caudate-putamen neurons, an 85-pS inwardly rectifying K+ channel, which was previously found to be modulated by D2-like dopamine receptors, was blocked by externally applied BaCl2 or CsCl. 2. At concentrations between 100 and 500 microM, Ba2+ blockade was voltage dependent, with a greater block at hyperpolarized voltages, in a manner consistent with blockade of the channel pore. Single-channel currents were flickery, with intervening periods of more complete blockade, and block appeared to be time dependent, with an estimated electrical distance of 0.24 and an apparent dissociation constant of 205 microM at 0 mV. 3. At concentrations between 1 and 3 mM, Cs+ blockade was similarly voltage dependent, but without periods of longer blockade, with an electrical distance of 0.81 and an apparent dissociation constant of 625 microM at 0 mV. Cs+ could also permeate this channel at voltages near the K+ reversal potential. The current-voltage relationship displayed an anomalous negative slope conductance, in a manner inconsistent with a single-ion pore. 4. Smaller-conductance, dopamine-insensitive channels were blocked more potently by both Ba2+ and Cs+ than was the 85-pS channel, reflecting differences between inwardly rectifying K+ channels mediating resting conductance and those mediating dopamine receptor responses in striatal neurons.
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Y J
YJ
Lin
G J
GJ
Greif
J E
JE
Freedman
D000818:Animals; D001464:Barium / Q000378:metabolism / Q000494:pharmacology*; D002586:Cesium / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D018492:Dopamine Antagonists; D015221:Potassium Channels; D002586:Cesium; D001464:Barium; D004298:Dopamine