| 11050110 |
Kulik A, Nishimaru H, Ballanyi K: Role of bicarbonate and chloride in GABA- and glycine-induced depolarization and [Ca2+] i rise in fetal rat motoneurons in situ. Eur J Pharmacol. 1994 Aug 22;261(3):295-301.
Ca (2+) imaging and (perforated) patch recording were used to analyze the mechanism of GABA- and glycine-induced depolarizations in lumbar motoneurons of spinal cord slices from fetal rats. In fura-2 ester-loaded cells, the agonist-induced depolarizations increased [Ca (2+)](i) by up to 100 nm. The GABA- and glycine-evoked [Ca (2+)](i) transients were suppressed by bicuculline and strychnine, respectively. Their magnitude decreased by approximately 50% between embryonic days 15.5 and 19.5. The [Ca (2+)](i) increases were abolished by Ca (2+)-free superfusate and attenuated by approximately 65% by nifedipine, showing that the responses were mediated by voltage-activated Ca (2+) channels. The [Ca (2+)](i) rises were potentiated by > 300% immediately after removal of Cl (-) from the superfusate but recovered to values of 50-200% of control during repeated agonist administration in Cl (-)-free saline. Bumetanide gradually suppressed the [Ca (2+)](i) increases by > 75%. Subsequent removal of Cl (-) reconstituted the responses and increased, upon repeated agonist application, the peak [Ca (2+)](i) rises to values above control. Removal of HCO (3)(-) from the Cl (-)-free (bumetanide-containing) superfusate reversibly abolished both the agonist-induced [Ca (2+)](i) rises and depolarizations that were reestablished by formate anions. In Cl (-)-containing superfusate, removal of HCO (3)(-) decreased both the peak and duration of the agonist-evoked membrane depolarization and [Ca (2+)](i) response. Our findings show that HCO (3)(-) efflux has a major contribution to depolarizations mediated by GABA (A) and glycine receptor-coupled anion channels in prenatal neurons. We hypothesize that the HCO (3)(-)-dependent depolarizing component, which is likely to produce an intracellular acidosis, might play an important role during the early postnatal period when the Cl (-)-dependent component gradually shifts to hyperpolarization. |
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