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Divalent cations activate small- (SK) and large-conductance (BK) channels in mouse neuroblastoma cells: selective activation of SK channels by cadmium

✍ Scribed by T. Leinders; R. G. D. M. Kleef; H. P. M. Vijverberg


Publisher
Springer
Year
1992
Tongue
English
Weight
686 KB
Volume
422
Category
Article
ISSN
0031-6768

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✦ Synopsis


Effects of Cd 2+, CO 2+ , Fe 2+ and Mg 2+ (1 ~M and 100 ~tM) and Pb 2+ (1 ~tM and 90 ~tM) on singlechannel properties of the small-conductance (SK) and large-conductance (BK) Ca2+-activated K + channels were investigated in inside-out patches of N1E-115 mouse neuroblastoma cells. Cd 2+, Co 2+ and Pb 2+, but not Fe 2+ and Mg 2+, cause SK channel opening. The potency of the metals in enhancing the SK channel-open probability follows the sequence Cd 2+ ~ Pb 2+ >Ca 2+ >Co 2+ -> Mg 2+ , Fe z+ . The four metals that cause SK channel opening are equipotent in enhancing the opening frequency of SK channels. The BK channel is activated by Pb 2+ and Co 2+ , whereas Cd z+ , Fe z+ and Mg 2+ are ineffective. The potency of the metals in enhancing BK channel-open probability, open time and opening frequency follows the sequence Pb 2+ >Ca 2+ >Co 2+ ~>Cd 2+ , Mg 2+ , Fe z+ . The results show that SK channels are much more sensitive to Cd 2+ than BK channels and indicate that Cd 2+ is a selective agonist of SK channels. It is concluded that the various metal ions bind to the same regulatory site(s) at which Ca 2+ activates the SK and BK channels under physiological conditions. The different potency sequences of metal ions with respect to BK and SK channel activation indicate that the regulatory sites of these CaZ+-activated K + channeles have distinct chemical and physical properties.