Calcium-mediated intracellular messengers modulate the serotonergic effects on axonal excitability
| Autor: | Wise Young, A.Z. Hassan, Y. Saruhashi |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Agonist Serotonin medicine.medical_specialty medicine.drug_class Action Potentials In Vitro Techniques Serotonergic Second Messenger Systems Internal medicine medicine Animals Protein Kinase Inhibitors Protein kinase C 5-HT receptor Chemistry General Neuroscience Quipazine Protein kinase inhibitor Axons Rats Serotonin Receptor Agonists Electrophysiology Endocrinology Spinal Cord Receptors Serotonin Calcium Female Serotonin Agonist medicine.drug |
| Zdroj: | Neuroscience. 81:959-965 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/s0306-4522(97)00219-4 |
| Popis: | We carried out experiments to investigate the mechanisms of serotonin-induced axonal excitability changes using isolated dorsal columns from young (seven to 11-day-old) Long-Evan's hooded rats. Conducting action potentials were activated by submaximal (50%) and supramaximal constant current electrical stimuli and recorded with glass micropipette electrodes. In experiment 1, to study Ca(2+)-mediated mechanisms, we superfused the preparations with Ringer solutions containing varying Ca2+ concentrations. Following superfusion with Ca(2+)-free Ringer solution for 4 h, we tested initial responses to serotonin agonists. Studies then were repeated after preparations had been washed for 1 h with Ringer solution containing 1.5 mM Ca2+ and 1.5 mM Mg2+. After 4 h superfusion of Ca(2+)-free Ringer solution, quipazine (a serotonin2A agonist, 100 microM) did not induce significant axonal excitability changes (amplitude change of 1.4 +/- 1.3%, percentage of predrug control level, +/-S.D., n = 6). A 100 microM concentration of 8-hydroxy-dipropylaminotetralin (a serotonin1A agonist) reduced response amplitudes by 36.3 +/- 4.2% (+/-S.D., P0.0005, n = 7) and prolonged latencies by 22.3 +/- 4.3% (+/-S.D., P0.0005, n = 7). Application of serotonin (100 microM) decreased amplitudes by 6.6 +/- 5.0% (+/-S.D., P0.05, n = 6). Extracellular calcium concentration ([Ca2+]e) was measured at various depths in the dorsal column with ion-selective microelectrodes. Four hours' superfusion with Ca(2+)-free Ringer solution reduced [Ca2+]e to less than 0.1 mM in dorsal columns. In 1.5 mM Ca2+ Ringer solution, quipazine increased the amplitudes by 38.3 +/- 5.8% (P0.0005, n = 6). Likewise, serotonin increased the amplitudes by 13.8 +/- 4.9% (P0.005, n = 6). In contrast however, 8-hydroxy-dipropylaminotetralin still reduced amplitudes by 35.0 +/- 6.4% (P0.0005, n = 7) and prolonged latencies by 24.1 +/- 4.5% (P0.0005, n = 7). In experiment 2, we investigated calcium-dependent and cAMP-mediated protein kinase signalling pathways to evaluate their role as intracellular messengers for serotonin2A receptor activation. Two protein kinase inhibitors, 50 microM H7 (an inhibitor of protein kinase C and c-AMP dependent protein kinase) and 100 microM D-sphingosine (an inhibitor of protein kinase A and C) effectively eliminated the excitatory effects of the serotonin2A agonist. 100 microM cadmium (a Ca2+ channel blocker) also blocked the effects of quipazine. Neither these protein kinase inhibitors nor cadmium alone affected action potential amplitudes. These results suggest that replacing Ca2+ with Mg2+ blocks the excitatory effects of quipazine but does not prevent the inhibitory effects of 8-hydroxy-dipropylaminotetralin, and calcium-mediated protein kinase mechanisms modulate axonal excitability changes induced by serotonin and its agonist. |
| Databáze: | OpenAIRE |
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