Histamine enhances voltage-gated potassium currents of ON bipolar cells in macaque retina.
OBJECTIVE
The goal was to understand the functions of retinopetal axons containing histamine. In prior work, type 3 histamine receptors (HR3) have been localized to the tips of ON bipolar cell dendrites in macaque retinas. Voltage-gated potassium channels have also been localized to bipolar cell dendrites, and the hypothesis tested in the present study was that these are modulated by histamine.


METHODS
Whole-cell recordings of potassium currents were made from bipolar cells in slice preparations of macaque retina. In voltage-clamp mode, the cells were held at -60 mV and stepped to values from -60 to 80 mV. Recordings of the membrane potential were also made in current-clamp mode. Histamine, the HR3 agonist (R) alpha-methylhistamine (RAMH), tetraethyl ammonium (TEA), and 4-aminopyridine (4-AP) were applied in the superfusate.


RESULTS
Histamine produced a dose-dependent increase in potassium currents in a subset of bipolar cells. At 5 microM, histamine increased the currents by 15% or more in the ON bipolar cells but not in the OFF bipolar cells. RAMH at 5 microM increased the amplitude of the potassium currents in the ON bipolar cells. In 10 mM TEA, potassium currents were reduced in all the bipolar cells, and there was no effect of histamine. Histamine hyperpolarized the resting membrane potential of the ON bipolar cells by 5 mV.


CONCLUSIONS
By enhancing potassium currents in the ON bipolar cells, histamine is expected to reduce the amplitude of the light responses and limit their duration. The hyperpolarization of the resting membrane potential would also reduce neurotransmitter release at their output synapses.
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77225, USA.
Yong-Chun
YC
Yu
Hiromasa
H
Satoh
Samuel M
SM
Wu
David W
DW
Marshak
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008761:Methylhistamines / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000187:drug effects* / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology
D017442:Histamine Agonists; D008761:Methylhistamines; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D018100:Receptors, Histamine H3; D019789:Tetraethylammonium; D006632:Histamine; D015761:4-Aminopyridine; D011188:Potassium