© 1999 American Heart Association, Inc.
Original Contribution |
Proadrenomedullin N-Terminal 20 Peptide Hyperpolarizes the Membrane by Activating an Inwardly Rectifying K+ Current in Differentiated PC12 Cells
From the Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Correspondence to Koji Takano, MD, PhD, Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112-8688, Japan.
Abstract—The mechanism of
proadrenomedullin N-terminal 20 peptide (PAMP)–induced inhibition of
catecholamine release from adrenergic nerve was
investigated in nerve growth factor–treated PC12 cells that have
differentiated characteristics somewhat similar to
noradrenergic neurons. The effect of PAMP on the
excitability of these cells was investigated with the use of perforated
whole-cell clamp. PAMP hyperpolarized the membrane by increasing a
K+ conductance in a dose-dependent manner. The
current-voltage relationship (I-V) relationship of the
PAMP-induced K+ conductance exhibited inward-going
rectification. The activation was abolished by microinjecting GDPßS
into the cells or pretreating the cells with pertussis toxin. These
results indicate that a pertussis toxin–sensitive G protein is
involved in the signal transduction. The PAMP-induced activation of the
K+ conductance was attenuated by microinjecting antibody
against the carboxyl terminus of G
i3, but it was not
influenced by microinjecting antibody against the common carboxyl
termini of Gi1 and Gi2, which indicated
that the G protein coupling the PAMP receptor to the inwardly
rectifying K+ current is Gi3. The
PAMP-induced hyperpolarization may inhibit the
catecholamine release from the neurons by attenuating the
action potential frequency.
Key Words: channel • PC12 cell • hypertension