TY - JOUR
T1 - Serotonin and protein kinase C modulation of a rat brain inwardly rectifying K+ channel expressed in Xenopus oocytes
AU - DiMagno, Lisa
AU - Dascal, Nathan
AU - Davidson, Norman
AU - Lester, Henry A.
AU - Schreibmayer, Wolfgang
PY - 1996
Y1 - 1996
N2 - In Xenopus laevis oocytes injected with rat brain poly(A)+ RNA, perfusion with a high-K+ solution (96 mM KCl generated an inward current (I(HK)) which was absent in water-injected oocytes. Part of I(HK) was blocked by low concentrations of Ba2+ (half-maximal inhibitory concentration, IC50: 4.2 ± 0.5 μM). When serotonin (5-HT) was applied to these oocytes a transient inward oscillating Cl- current arising from activation of Ca2+-dependent Cl- channels, I(Cl(CA)), was observed. When this response decayed, a 30% reduction of I(HK) could be detected. Electrophysiological characterization of the K+ channel down-modulated by 5-HT revealed that it is an inward rectifier. Antisense suppression experiments revealed that the 5-HT(2C) receptor mediates the down-modulatory effect of 5-HT. The nature of the modulatory pathway was investigated by application of phorbol esters and intracellular injection of protein kinase C (PKC) inhibitors, ethylenebis (oxonitrilo)tetraacetate (EGTA) and inositol 1, 4, 5-trisphosphate. The results demonstrate that PKC is responsible for the down-modulatory effect.
AB - In Xenopus laevis oocytes injected with rat brain poly(A)+ RNA, perfusion with a high-K+ solution (96 mM KCl generated an inward current (I(HK)) which was absent in water-injected oocytes. Part of I(HK) was blocked by low concentrations of Ba2+ (half-maximal inhibitory concentration, IC50: 4.2 ± 0.5 μM). When serotonin (5-HT) was applied to these oocytes a transient inward oscillating Cl- current arising from activation of Ca2+-dependent Cl- channels, I(Cl(CA)), was observed. When this response decayed, a 30% reduction of I(HK) could be detected. Electrophysiological characterization of the K+ channel down-modulated by 5-HT revealed that it is an inward rectifier. Antisense suppression experiments revealed that the 5-HT(2C) receptor mediates the down-modulatory effect of 5-HT. The nature of the modulatory pathway was investigated by application of phorbol esters and intracellular injection of protein kinase C (PKC) inhibitors, ethylenebis (oxonitrilo)tetraacetate (EGTA) and inositol 1, 4, 5-trisphosphate. The results demonstrate that PKC is responsible for the down-modulatory effect.
KW - 5-HT(2C) receptor
KW - Brain
KW - Heterologous expression
KW - Inward rectifying potassium channel
KW - Modulation
KW - PKC
KW - Serotonin
KW - Xenopus laevis oocytes
UR - http://www.scopus.com/inward/record.url?scp=0029876641&partnerID=8YFLogxK
U2 - 10.1007/BF02207270
DO - 10.1007/BF02207270
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AN - SCOPUS:0029876641
SN - 0031-6768
VL - 431
SP - 335
EP - 340
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
IS - 3
ER -