The Journal of Neurophysiology Vol. 84 No. 5 November 2000, pp. 2541-2551
Copyright ©2000 by the American Physiological Society
Activation of Protein Kinase C by Oxytocin-Related Conopressin
Underlies Pacemaker Current in Lymnaea Central
Neurons
Paul F.
Van Soest,
Johannes
C.
Lodder, and
Karel S.
Kits
Department of Neurophysiology, Research Institute Neurosciences,
Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
Van Soest, Paul F.,
Johannes
C. Lodder, and
Karel S. Kits.
Activation of Protein Kinase C by Oxytocin-Related Conopressin
Underlies Pacemaker Current in Lymnaea Central
Neurons. J. Neurophysiol. 84: 2541-2551, 2000. The vasopressin/oxytocin-related neuropeptide
Lys-conopressin activates two pacemaker currents in central neurons of
the mollusk Lymnaea stagnalis. A high-voltage-activated
current (I-HVA) is activated at potentials greater than 
40
mV and resembles pacemaker currents found in many molluscan neurons. A
low-voltage-activated current (I-LVA) activates throughout
the range of 90 to 0 mV. Based on sequence homologies,
Lymnaea conopressin receptors are thought to couple to
Q-type G proteins and protein kinase C (PKC). Alternatively,
agonist-induced pacemaker currents in molluscan neurons have
traditionally been attributed to cAMP-dependent protein kinase (PKA)
activation. Accordingly, this study aimed at resolving possible
involvement of cAMP/PKA and diacylglycerol/PKC in the conopressin
response. Injection of cAMP into anterior lobe neurons induced a slow
inward current with a voltage dependence resembling that of
ILVA (and not
IHVA). However, lack of effect of the
phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine and the absence
of cross-desensitization between cAMP and conopressin suggest that
neither current is dependent on intracellular cAMP. The PKC-activating
phorbol ester 12-O-tetradecanoylphorbol 13-acetate (but not
inactive phorbol 12-myristate 13-acetate) mimicked activation of
IHVA, but not
ILVA, and occluded subsequent responses to conopressin. Activation of
IHVA was blocked by general protein
kinase inhibitors and the PKC-inhibitor GF-109203X. Modulation of the
calcium buffering capacity of the pipette medium did not affect the
conopressin response, suggesting that calcium dynamics are not of major
importance. We conclude that conopressin activates the ion channels
carrying ILVA and
IHVA through different
second-messenger cascades and that PKC-dependent phosphorylation
underlies activation of IHVA.
