Bradykinin inhibits M current via phospholipase C and Ca2+ release from IP3-sensitive Ca2+ stores in rat sympathetic neurons.
A variety of intracellular signaling pathways can modulate the properties of voltage-gated ion channels. Some of them are well characterized. However, the diffusible second messenger mediating suppression of M current via G protein-coupled receptors has not been identified. In superior cervical ganglion neurons, we find that the signaling pathways underlying M current inhibition by B2 bradykinin and M1 muscarinic receptors respond very differently to inhibitors. The bradykinin pathway was suppressed by the phospholipase C inhibitor U-73122, by blocking the IP3 receptor with pentosan polysulfate or heparin, and by buffering intracellular calcium, and it was occluded by allowing IP3 to diffuse into the cytoplasm via a patch pipette. By contrast, the muscarinic pathway was not disrupted by any of these treatments. The addition of bradykinin was accompanied by a [Ca2+]i rise with a similar onset and time to peak as the inhibition of M current. The M current inhibition and the rise of [Ca2+]i were blocked by depletion of Ca2+ internal stores by thapsigargin. We conclude that bradykinin receptors inhibit M current of sympathetic neurons by activating phospholipase C and releasing Ca2+ from IP3-sensitive Ca2+ stores, whereas muscarinic receptors do not use the phospholipase C pathway to inhibit M current channels.
Cruzblanca
H
H
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Koh
D S
DS
Hille
B
B
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
D015220:Calcium Channels; D011976:Receptors, Muscarinic; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium