Neuropeptide Y reduces calcium current and inhibits acetylcholine release in nodose neurons via a pertussis toxin-sensitive mechanism.
1. The effect of neuropeptide Y (NPY) on voltage-dependent calcium currents was studied in acutely dissociated rat vagal afferent (nodose) neurons by the use of both intracellular single-electrode and whole-cell patch-clamp techniques. 2. Nodose neurons exhibited three calcium current components similar to the transient low-threshold (T), slowly inactivating high-threshold (L), and the transient high-threshold (N) currents previously described in dorsal root ganglion neurons (Nowycky et al. 1985). The characteristics of calcium current components were similar for the two recording techniques except that the inactivation time constants (tau i) were two- to threefold larger at 22 degrees C (whole-cell patch clamp) than at 35 degrees C (single-electrode voltage clamp). 3. NPY (0.1-100 nM, ED50 4 nM) produced a concentration-dependent reduction in calcium currents with the use of both recording techniques. NPY (100 nM) had no effect on T and L currents but reduced the combined N/L current 31 +/- 6% in 47% of the cells tested. Current traces were also analyzed by multiexponential curve fitting to determine amplitudes and inactivation time constants (tau i). NPY selectively reduced the amplitude of the curve-fitted N current component 45 +/- 8% but had no effect on any of the tau i. The effect of NPY to reduce calcium current was blocked in the presence of gadolinium (1 microM), a putative N channel antagonist. Pretreatment of cultures with pertussis toxin (PTX) (100 ng/ml) for 16-24 h blocked the effect of NPY. 4. NPY reduced the peak current without changing the voltage dependence of the peak current-voltage relation.(ABSTRACT TRUNCATED AT 250 WORDS)
Wiley
J W
JW
Department of Neurology, University of Michigan, Medical Center, Ann Arbor 48109-0362.
Gross
R A
RA
Lu
Y X
YX
Macdonald
R L
RL
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000494:pharmacology*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D014630:Vagus Nerve / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D009478:Neuropeptide Y; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium