Cyclic AMP-mediated long-term facilitation of glycinergic transmission in developing spinal dorsal horn neurons.
cAMP is known to regulate neurotransmitter release via protein kinase A (PKA)-dependent and/or PKA-independent signal transduction pathways at a variety of central synapses. Here we report the cAMP-mediated long-lasting enhancement of glycinergic transmission in developing rat spinal substantia gelatinosa neurons. Forskolin, an adenylyl cyclase activator, elicited a long-lasting increase in the amplitude of nerve-evoked glycinergic inhibitory postsynaptic currents (IPSCs), accompanied by a long-lasting decrease in the paired-pulse ratio in immature substantia gelatinosa neurons, and this forskolin-induced increase in glycinergic IPSCs decreased with postnatal development. Forskolin also decreased the failure rate of glycinergic IPSCs evoked by minimal stimulation, and increased the frequency of glycinergic miniature IPSCs. All of these data suggest that forskolin induces the long-lasting enhancement of glycinergic transmission by increasing in the presynaptic release probability. This pre-synaptic action of forskolin was mediated by hyperpolarization and cyclic nucleotide-activated cation channels and an increase in intraterminal Ca(2+) concentration but independent of PKA. The present results suggest that cAMP-dependent signal transduction pathways represent a dynamic mechanism by which glycinergic IPSCs could potentially be modulated during postnatal development.
Choi
In-Sun
IS
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
Nakamura
Michiko
M
Cho
Jin-Hwa
JH
Park
Hye-Mi
HM
Kim
Sang-Jung
SJ
Kim
Jun
J
Lee
Jong-Ju
JJ
Choi
Byung-Ju
BJ
Jang
Il-Sung
IS
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005998:Glycine / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000502:physiology; D013376:Substantia Gelatinosa / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018009:Receptors, Glycine; D005576:Colforsin; D000242:Cyclic AMP; D005998:Glycine