title: Potassium currents operated by thyrotrophin-releasing hormone in dissociated CA1 pyramidal neurones of rat hippocampus.
abstract: 1. Membrane currents activated by thyrotrophin-releasing hormone (TRH) were investigated in the dissociated rat hippocampal CA1 pyramidal neurone using the nystatin perforated patch recording configuration. 2. Under current-clamp condition, TRH caused a transient hyperpolarization accompanied by a decrease of firing activity and a successive long-lasting depolarization. The latter induced a blockade of firing. 3. When neurones were held at a holding potential (VH) of -40 mV under voltage clamp, TRH elicited a transient outward current with an increase in the membrane conductance, which was followed by a sustained inward current with a decrease in membrane conductance. The inactive TRH metabolite, TRH free acid, did not induce any currents. 4. The reversal potential of TRH-induced outward current (ETRH) was close to the K+ equilibrium potential (EK). The change in ETRH for a 10-fold change in extracellular K+ concentration was 56.4 mV, indicating that the membrane behaves like a K+ electrode in the presence of TRH. On the other hand, the TRH-induced inward current was due to suppression of a slow inward current relaxation during hyperpolarizing voltage commands to -50 mV from a VH of -40 mV, indicating the suppression of the voltage- and time-dependent component of the K+ current (M-current). 5. The TRH-induced outward current (ITRH) increased in a concentration-dependent manner over the concentration range 10(-8)-10(-6) M. The half-maximum concentration was 7.4 x 10(-8) M and the Hill coefficient was 1.5. 6. The TRH-induced outward current (ITRH) was antagonized by K+ channel blockers such as tetraethylammonium (TEA), 4-aminopyridine (4-AP) and Ba2+ in a concentration-dependent manner. ITRH was insensitive to both apamin and iberiotoxin. 7. The first application of TRH to neurones perfused with Ca(2+)-free external solution containing 2 mM EGTA could induce ITRH but the TRH response diminished dramatically with successive applications. Intracellular perfusion with a Ca2+ chelator, 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), also diminished the TRH response. 8. The depletion of Ca2+ from the intracellular Ca2+ store by thapsigargin blocked the TRH response without affecting the caffeine response. Pretreatment with Li+ significantly enhanced ITRH, suggesting that ITRH is involved in the elevation of intracellular free Ca2+ released from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store site but not from the caffeine-sensitive one. 9. Staurosporine, a protein kinase C (PKC) inhibitor, suppressed ITRH in a concentration-dependent manner (the half-maximum inhibitory concentration (IC50), was 2.45 x 10(-8) M).(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ebihara
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013973:Thyrotropin-Releasing Hormone; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D019311:Staurosporine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium