Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex.
We examined the mechanisms of kainate (KA) induced modulation of GABA release in rat prefrontal cortex. Pharmacologically isolated IPSCs were recorded from visually identified layer II/III pyramidal cells using whole-cell patch clamp techniques. KA produced an increase in evoked IPSC amplitude at low nanomolar concentrations (100-500 nM). The frequency but not the amplitude of miniature (m) IPSCs was also increased. The GluR5 subunit selective agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) caused an increase in mIPSC frequency whereas (3S,4aR,6S,8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884), a selective GluR5 subunit antagonist, inhibited this facilitation. Philanthotoxin-433 (PhTx) blocked the effect of KA, indicating involvement of Ca(2+)-permeable GluR5 receptors. No IPSC facilitation was seen when Ca(2+) was omitted from the bathing solution. Facilitation was observed when slices were preincubated in ruthenium red or high concentrations of ryanodine, but was inhibited with application of thapsigargin. The IP3 receptor (IP3R) antagonists diphenylboric acid 2-amino-ethyl ester (2-APB) (15 microM) and Xestospongin C (XeC) blocked IPSC facilitation. These results show that activation of KA receptors (KARs) on GABAergic nerve terminals results is linked to intracellular Ca(2+) release via activation of IP3, but not ryanodine, receptors. This represents a new mechanism of presynaptic modulation whereby Ca(2+) entry through Ca(2+)-permeable GluR5 subunit containing KARs activates IP3Rs receptors leading to an increase in GABA release.
Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Seena S
SS
Mathew
John J
JJ
Hablitz
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology*; D047028:Macrocyclic Compounds / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D001896:Boron Compounds; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D018733:Nicotinic Antagonists; D010080:Oxazoles; D011073:Polyamines; C511704:xestospongin C; C034092:delta-philanthotoxin; C109986:2-aminoethoxydiphenyl borate; D007608:Kainic Acid; D002118:Calcium