Angiotensin II-induced stimulation of voltage-dependent Ca2+ currents in an adrenal cortical cell line.
Biochemical studies suggest that stimulation of aldosterone secretion by angiotensin II involves activation of voltage-dependent Ca2+ channels. We used an adrenocortical cell line (Y1) to study the effect of angiotensin II on transmembranous currents. The hormone (1 nM to 1 microM) caused depolarization of the plasma membrane (from -35 to 10 mV) and elicited repetitive action potentials. Using the whole-cell clamp technique, we identified two types of voltage-dependent Ca2+ currents which differed with respect to their threshold potential and time course of inactivation. Angiotensin II (1 nM to 1 microM) stimulated a slowly inactivating Ca2+ current on average up to 1.7-fold whereas a fast inactivating Ca2+ current remained almost unaffected by the hormone. Ca2+ currents were not influenced by forskolin (1 microM) or intracellularly applied cAMP (50 microM). Pretreatment of cells with pertussis toxin abolished the hormonal stimulation of the slowly inactivating Ca2+ current but was without effect on control currents. The toxin ADP-ribosylated a single membranous peptide of 40 kd Mr. An antiserum raised against a synthetic peptide corresponding to a region common to all sequenced alpha-subunits of guanine nucleotide-binding proteins (G-proteins) and an antiserum raised against a peptide corresponding to a region of alpha-subunits of Gi-like G-proteins reacted with membranous 40 kd peptides, whereas an antiserum raised against a synthetic peptide corresponding to a region specific for the alpha-subunit of the G-protein, G0, failed to recognize a peptide in the 39 to 40 kd region.(ABSTRACT TRUNCATED AT 250 WORDS)
Hescheler
J
J
II. Physiologisches Institut, Universität des Saarlandes, Homburg/Saar, FRG.
Rosenthal
W
W
Hinsch
K D
KD
Wulfern
M
M
Trautwein
W
W
Schultz
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology; D005711:Gallopamil / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D037342:Pertussis Toxin; D013779:Tetrodotoxin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007473:Ion Channels; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D005711:Gallopamil; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium