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Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium‐dependent action potentials
Author(s) -
Kamp Timothy J.,
Miller Richard J.,
Sanguinetti Michael C.
Publication year - 1985
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.1476-5381.1985.tb08889.x
Subject(s) - stimulation , calcium , dihydropyridine , cardiac action potential , action (physics) , chemistry , neuroscience , pharmacology , medicine , electrophysiology , biology , physics , repolarization , quantum mechanics
1 Calcium (Ca 2+ )‐dependent action potentials were recorded from 22 mM potassium (K + )‐depolarized guinea‐pig papillary muscle at several different pacing frequencies in the absence and presence of CGP 28 392 (10 μM), a Ca 2+ channel agonist. The maximum upstroke velocity ( max ) of the slow response action potential was measured to determine relative changes in Ca 2+ current as a function of pacing frequency. 2 CGP 28 392 increased max more than two fold at low rates of stimulation (1 or 12 pulses min −1 ), but had no significant effect on max during rapid pulsing (200 pulses min −1 ). 3 The enhancement of max was dependent upon extracellular [K + ]. Increasing extracellular [K + ] from 22 mM to 27 mM suppressed the frequency‐dependent agonist effects and increased the antagonist effects on max . 4 These results indicate that CGP 28 392 is a partial Ca 2+ ‐channel agonist and suggest that its effects on Ca 2+ current are voltage‐dependent.