ISSN:
1573-6830
Keywords:
mercury
;
copper
;
zinc
;
lanthanum
;
lanthanides
;
GABA receptor channel
;
chloride channel
;
dorsal root ganglion
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
Notes:
Summary 1. The GABAA receptor-chloride channel complex has been shown to be modulated by a variety of chemicals. Scores of chemicals with diverse and unrelated structures augment the GABA-induced chloride current, while some other chemicals suppress the current. Certain heavy metals and a variety of polyvalent cations increase or decrease the current in a potent and efficacious manner. 2. We have studied the mechanisms whereby mercury, copper, zinc, and lanthanides modulate the GABA system by whole-cell and single-channel patch clamp techniques as applied to the rat dorsal root ganglion neurons in primary culture. 3. Mercuric chloride augmented the GABA-induced current to 115% of control at 0.1 µM and to 270% of control at 100 µM. It also generated a slowly developing inward current carried by a variety of ions. In contrast, methylmercury suppressed the GABA-induced current. The potent stimulation of the GABA system by mercuric chloride is deemed important in mercury intoxication. 4. Copper and zinc suppressed the GABA-induced current with an EC50 of 16 and 19 µM, respectively. They bound to a common site on the external surface of the GABA receptor-channel complex. 5. Lanthanum augmented the GABA-induced current with an EC50 of 230 µM by increasing the affinity of the receptor for GABA. It bound to a site on or near the external surface of the GABA receptor-channel complex which is different from the sites for GABA, barbiturates, benzodiazepines, picrotoxin, and copper/zinc. 6. Six other lanthanides with larger atomic numbers also exerted the same stimulatory effect with their efficacies increasing with the atomic number. 7. Single-channel analyses have revealed that the augmentation of whole-cell current by terbium, a lanthanide, is due to three actions: an increase in the overall mean open time, a decrease in the overall mean closed time, and an increase in the overall mean burst time.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02088671
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