A comparison of effects of SKF 525-A and procaine on excitation-contraction coupling in single crayfish muscle fibers.
The effects of beta-diethylaminoethyldiphenylpropylacetate hydrochloride (SKF 525-A) on excitation-contraction coupling and Ca-dependent electrogenesis are compared to those of procaine. At pH 7.2, SKF 525-A and procaine occur essentially (greater that 97%) as a free base and as a cation, respectively. At this pH, SKF 525-A elicited tension development, blocked K-induced contractures and the K-induced repriming of caffeine contractions, potentiated caffeine-induced tensions, inhibited the procaine-induced spikes and twitches and, depending on the concentration, either potentiated (25-50 muM) or depressed (greater than 100 muM) the tensions associated with the graded membrane electrogenesis. At the same pH, procaine blocked the contractions elicited by SKF 525-A, by high K media, by the graded electrogenesis and by caffeine, and converted the graded membrane responses into all-or-none spikes. It is proposed that SKF 525-A as a free base 1) inhibits membrane Ca activation more effectively than it depresses K conductance and 2) is synergistic with caffeine in reducing the effectiveness of Ca sequestration by the sarcoplasmic reticulum. Procaine as a cationic molecule is thought to depress K activation more than Ca activation during depolarization and to block the release of Ca ions from the sarcoplasmic reticulum.
D000818:Animals; D003400:Astacoidea / Q000187:drug effects* / Q000502:physiology; D002110:Caffeine / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D004558:Electric Stimulation; D009119:Muscle Contraction / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011335:Proadifen / Q000494:pharmacology*; D011343:Procaine / Q000494:pharmacology*
D002110:Caffeine; D011343:Procaine; D011335:Proadifen; D011188:Potassium