Calmodulin antagonists and protein phosphatase inhibitor okadaic acid fasten the 'run-up' of high-voltage activated calcium current in rat hippocampal neurones.
Voltage-activated Ca2+ channel currents were recorded from cultured rat hippocampal neurones using the whole-cell clamp technique with Ba2+ as a charge carrier. After breaking into the cell the amplitude of low-voltage activated Ca2+ channel current increased to a new steady value within 1 min whereas several minutes were required for a full development of the high-voltage activated current (IHVA). Pretreatment of cells with calmodulin antagonists (trifluoperazine or W-13) or protein phosphatase inhibitor, okadaic acid, fastened the development of IHVA. Trifluoperazine (6-40 microM) also increased IHVA when applied after breaking into the cell in standard external solution. Incubation of cells in the presence of permeable precursor of Ca2+ chelator, BAPTA, was without effect. The effects of all inhibitors studied allow to suggest that IHVA in intact cells is largely masked due to activity of calmodulin-activated protein phosphatase.
Mironov
S L
SL
Max-Planck Institute for Psychiatry, Planegg-Martinsried, F.R.G.
Lux
H D
HD
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011712:Pyramidal Tracts / Q000502:physiology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology*
D015220:Calcium Channels; D002147:Calmodulin; D004988:Ethers, Cyclic; D013449:Sulfonamides; D019319:Okadaic Acid; D014268:Trifluoperazine; D013779:Tetrodotoxin; D004533:Egtazic Acid; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D010749:Phosphoprotein Phosphatases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid