Growth hormone-releasing factor reduces voltage-gated Ca2+ channel current in rat GH3 cells.
The action of GRF on GH3 cell membrane was examined by patch electrode techniques. Under current clamp with patch electrode, spontaneous action potentials were partially to totally eliminated by application of GRF. In the case of partial elimination, the duration of remaining spontaneous action potentials was prolonged and the amplitude of afterhyperpolarization was decreased. The evoked action potential in the cells which did not show spontaneous action potentials was also eliminated by GRF. In order to examine what channels were affected by GRF, voltage-clamp analysis was performed. It was revealed that voltage-gated Ca2+ channel current and Ca2+-induced K+ channel current were decreased by GRF, while voltage-gated Na+ channel and delayed K+ channel were not affected. The decrease of Ca2+-induced K+ channel current was considered to be a consequence of the decrease of voltage-gated Ca2+ channel current. Therefore it is likely that the effect of GRF on GH3 cells was due to the block of voltage-gated Ca2+ channels. The elimination of action potential under current clamp corresponded to the block of voltage-gated Ca2+ channels and the prolongation of action potential could be explained by the decrease of Ca2+-induced K+ channel current. The amplitude decrease of afterhyperpolarization could also be explained by the reduction of Ca2+-induced K+ channel current. Thus the results under current clamp well coincide with the results under voltage clamp. Hormone secretion from GH3 cells was not stimulated by GRF. However, the finding that GRF solely blocked voltage-gated Ca2+ channel suggested the specific action of GRF on GH3 cell membranes.
N
N
Yamashita
Y
Y
Takuwa
E
E
Ogata
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004553:Electric Conductivity / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005910:Glioma; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats
D007473:Ion Channels; D013007:Growth Hormone-Releasing Hormone; D002118:Calcium