Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells.
Upon exposure to dopamine, cultured teleost retinal horizontal cells become more responsive to the putative photoreceptor neurotransmitter L-glutamate and to its analog kainate. We have recorded unitary and whole-cell currents to determine the mechanism by which dopamine enhances ion channels activated by these agents. In single-channel recordings from cell-attached patches with agonist in the patch pipette, the frequency of 5- to 10-pS unitary events, but not their amplitude, increased by as much as 150% after application of dopamine to the rest of the cell. The duration of channel openings also increased somewhat, by 20-30%. In whole-cell experiments, agonists with and without dopamine were applied to voltage-clamped horizontal cells by slow superfusion. Analysis of whole-cell current variance as a function of mean current indicated that dopamine increased the probability of channel opening for a give agonist concentration without changing the amount of current passed by an individual channel. For kainate, noise analysis additionally demonstrated that dopamine did not alter the number of functional channels. Dopamine also increased a slow spectral component of whole-cell currents elicited by kainate or glutamate, suggesting a change in the open-time kinetics of the channels. This effect was more pronounced for currents induced by glutamate than for those induced by kainate. We conclude that dopamine potentiates the activity of horizontal cell glutamate receptors by altering the kinetics of the ion channel to favor the open state.
Biological Laboratories, Harvard University, Cambridge, MA 02138.
A G
AG
Knapp
K F
KF
Schmidt
J E
JE
Dowling
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006220:Haloperidol / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010471:Perches; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D007473:Ion Channels; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D006220:Haloperidol; D007608:Kainic Acid; D004298:Dopamine