ISSN:
1432-2013
Schlagwort(e):
Calcium channels
;
Calcium-activated potassium current
;
Patch-clamp technique
;
Posterior pituitary
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract The effects of tetrandrine, a bis-benzyl-isoquinoline alkaloid, on voltage-gated Ca2+ currents (I Ca) and on Ca2+-activated K+ current (I K(Ca)) and channels in isolated nerve terminals of the rat neurohypophysis were investigated using patch-clamp techniques. The non-inactivating component of I Ca was inhibited by external tetrandrine in a voltage- and dose-dependent manner, with an IC50=10.1 μM. I K(Ca) was elicited by depolarizations when approximately 10 μM Ca2+ was present on the cytoplasmic side. Only externally applied tetrandrine, at 1 μM, decreased the amplitude of I K(Ca), whereas the fast inward Na+ current and transient outward K+ current were not affected. Tetrandrine, applied to the extracellular side of outside-out patches excised from the nerve terminals, induced frequent and short closures of single type II, maxi-Ca2+-activated K+channels. Tetrandrine decreased the channel-open probability, within bursts, with an IC50=0.21 μM. Kinetic analysis of the channel activity showed that the open-time constant decreased linearly with increasing tetrandrine concentrations (0.01–3 μM), giving an association rate constant of 8.8×108 M−1s−1, whereas the arithmetic mean closed time did not change, giving a dissociation rate constant of 136.6s−1. These results show that tetrandrine is a high-affinity blocker of the type II, maxi-Ca2+-activated K+ channel of the rat neurohypophysial terminals.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00375051
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