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. 1981 Sep;74(1):87–95. doi: 10.1111/j.1476-5381.1981.tb09958.x

Actions of verapamil, diltiazem and other divalent cations on the calcium-current of Helix neurones

N Akaike, AM Brown, K Nishi, Y Tsuda
PMCID: PMC2071873  PMID: 7272605

Abstract

1 Effects of organic Ca2+-antagonists, verapamil and diltiazem, and cations, Ni2+, Mn2+, Co2+ and La3+ on Ca2+ current (ICa) separated from other ionic currents in a Helix neurone were studied. A suction pipette technique which allows internal perfusion of the cell body and voltage clamp was used.

2 Verapamil and diltiazem (10-6-10-4 M) increased the threshold, and decreased both the amplitude and rate of rise of the soma Ca2+-spike. Both agents inhibited ICa over the entire range of the current-voltage (I-V) relationship dose-dependently, without shifting the threshold of the I-V relationship. Increases in external Ca2+ overcame the inhibitory action of the agents.

3 Divalent cations, Ni2+, Mn2+, Co2+ and the trivalent cation, La3+ inhibited ICa dose-dependently, but induced shifts of the I-V relationship to more positive voltages. The order of potency of inhibition of ICa among these cations was as follows; Ni2+ > La3+ > Mn2+ > Co2+.

4 Double reciprocal plots for peak ICa versus external Ca2+ concentrations in the presence or absence of both organic and inorganic Ca2+-antagonists intersect at the ordinate. Results indicate that both organic and inorganic Ca2+-antagonists compete for Ca2+ at the common binding site for Ca2+.

5 Internal application of the organic Ca2+-antagonists (10-4 M) inhibited ICa in a time-dependent manner to about 40-60% of the control. Ni2+, when applied internally, also depressed ICa.

6 The results provide evidence that organic Ca2+-antagonists occupy the binding site for Ca2+ in a competitive manner at the surface of the soma membrane of the Helix neurone, while divalent and trivalent cations, in addition to inhibiting ICa in a similar manner to the organic Ca2+-antagonists, change the surface charge of the soma membrane.

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Selected References

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