Zinc enhances ionic currents induced in skate Müller (glial) cells by the inhibitory neurotransmitter GABA.
We describe here a novel effect of zinc on GABA receptors of glial cells in the skate retina. The GABA-induced currents of skate Müller cells, the radial glia of the retina, are mediated by activation of GABA(A) receptors (GABAARS). In other parts of the nervous system, GABz*-)ediated currents are inhibited by zinc. However, in isolated, voltage-clamped Müller cells, coapplication of zinc (10 microM) and GABA (1 microM) resulted in enhancement of the GABA(A)R current. Surprisingly, zinc alone induced a current similar in many respects to that elicited by GABA, i.e. the reversal potential was the same as for the GABA-induced current, the current was blocked by bicuculline and picrotoxin, and the current-voltage relation obtained in the presence of 10 microM zinc was virtually identical to that obtained with 1 microM GABA. Both bicuculline and picrotoxin suppressed a current that was present with cells bathed only in Ringer, suggesting that some of the GABA channels were spontaneously open in the absence of externally applied GABA. This possibility was supported by cell-attached patch recordings. Under conditions in which potassium and calcium currents were suppressed, spontaneous channel activity was observed. Moreover, the frequency of these channel openings was greater when zinc was included in the pipette solution, and reduced when bicuculline was added. These findings suggest that zinc acts directly to enhance the GABA(A) receptor activity of the Müller cells, and raise the possibility that the subunit composition of the GABA(A)Rs of skate Müller cells differs from that of GABA(A)Rs identified previously in other neuronal and glial preparations.
Qian
H
H
Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA.
Malchow
R P
RP
Chappell
R L
RL
Ripps
H
H
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction; D012860:Skates, Fish; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D018756:GABA Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D015032:Zinc; D005680:gamma-Aminobutyric Acid