TY - JOUR
T1 - Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins
AU - Shapiro, Mark S.
AU - Wollmuth, Lonnie P.
AU - Hille, Bertil
N1 - Funding Information:
We gratefully acknowledge James Herrington for his expert assistance with the Ca*+ measurements. We thank DuPont Merck Pharmaceuticals for their kind gift of losartan and Fujisawa Chemical, USA Division, for their kind gift of FK-506. We thank Drs. A. Golard, S. Hehl, J. Herrington, and K. Mackie for reading the manuscript, and Don Anderson and Lea Miller for technical assistance. This work was supported by National Institutes of Health grant NS 08174, a McKnight Neuroscience Research Award,agrantfrom theW.M.KeckFoundation,andNRSAaward NS 07097 to M. S.
PY - 1994/6
Y1 - 1994/6
N2 - We characterized inhibition of N-type Ca2+ and M current K+ channels in rat superior cervical ganglion neurons by angiotensin II (angioII) using the patch clamp. Of 120 neurons, 97 showed inhibition of ICa (mean 32%), which was slow in onset and very slow to reverse under whole-cell recording conditions. This inhibition was blocked by the AT1 receptor antagonist losartan, attenuated by inclusion of 2 mM GDP-β-S in the pipette, mostly pertussis toxin insensitive, half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated; however, we detected no angioII-induced [Ca2+]i signal using the fluorescent indicator indo-1. IBa from cell-attached patches was reduced by bath-applied angioll (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioll in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioll, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.
AB - We characterized inhibition of N-type Ca2+ and M current K+ channels in rat superior cervical ganglion neurons by angiotensin II (angioII) using the patch clamp. Of 120 neurons, 97 showed inhibition of ICa (mean 32%), which was slow in onset and very slow to reverse under whole-cell recording conditions. This inhibition was blocked by the AT1 receptor antagonist losartan, attenuated by inclusion of 2 mM GDP-β-S in the pipette, mostly pertussis toxin insensitive, half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated; however, we detected no angioII-induced [Ca2+]i signal using the fluorescent indicator indo-1. IBa from cell-attached patches was reduced by bath-applied angioll (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioll in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioll, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.
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U2 - 10.1016/0896-6273(94)90447-2
DO - 10.1016/0896-6273(94)90447-2
M3 - Article
C2 - 7516687
AN - SCOPUS:0028283042
VL - 12
SP - 1319
EP - 1329
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -