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ACTIONS OF VERAPAMIL, DILTIAZEM AND OTHER DIVALENT CATIONS ON THE CALCIUM‐CURRENT OF Helix NEURONES
Author(s) -
AKAIKE N.,
BROWN A.M.,
NISHI K.,
TSUDA Y.
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb09958.x
Subject(s) - diltiazem , verapamil , chemistry , divalent , calcium , biophysics , inhibitory postsynaptic potential , stereochemistry , endocrinology , biology , organic chemistry
1 Effects of organic Ca 2+ ‐antagonists, verapamil and diltiazem, and cations, Ni 2+ , Mn 2+ , Co 2+ and La 3+ on Ca 2+ current (I Ca ) 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 Ca 2+ ‐spike. Both agents inhibited I Ca 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 Ca 2+ overcame the inhibitory action of the agents 3 Divalent cations, Ni 2+ , Mn 2+ , Co 2+ and the trivalent cation, La 3+ inhibited I Ca dose‐dependently, but induced shifts of the I‐V relationship to more positive voltages. The order of potency of inhibition of I Ca among these cations was as follows; Ni 2+ > La 3+ > Mn 2+ > Co 2+4 Double reciprocal plots for peak I Ca versus external Ca 2+ concentrations in the presence or absence of both organic and inorganic Ca 2+ ‐antagonists intersect at the ordinate. Results indicate that both organic and inorganic Ca 2+ ‐antagonists compete for Ca 2+ at the common binding site for Ca 2+5 Internal application of the organic Ca 2+ ‐antagonists (10 −4 m) inhibited I Ca in a time‐dependent manner to about 40–60% of the control. Ni 2+ , when applied internally, also depressed I Ca6 The results provide evidence that organic Ca 2+ ‐antagonists occupy the binding site for Ca 2+ in a competitive manner at the surface of the soma membrane of the Helix neurone, while divalent and trivalent cations, in addition to inhibiting I Ca in a similar manner to the organic Ca 2+ ‐antagonists, change the surface charge of the soma membrane.