Effects of excess K+ on carbachol-induced contractions in the guinea-pig tracheal muscle.
1. In smooth muscles isolated from the guinea-pig trachea, the effects of dihydropyridines, nifedipine and nicardipine on contractions produced by carbachol (Cch) were studied in normal (6 mM) and excess K+ concentration (60 mM). The tonic contraction produced by 1 microM Cch was highly dependent on the external Ca2+ concentration ([Ca2+]0) and was not significantly affected by cyclopiazonic acid or thapsigargin, Ca2+ uptake inhibitor. 2. [Ca2+]0-tension curves were steeper in the presence of 1 microM Cch (the Hill coefficient: 2.5) than in the presence of 60 mM K+ (Hill coefficient: 1.6) and their ED50 of Ca2+ was 0.16 and 0.39 mM, respectively. An increase of K+ to 60 mM in the presence of 1 microM Cch shifted the curve to the left roughly in parallel (ED50: 0.12 mM, Hill coefficient: 2.3). 3. [Ca2+]0-tension curve in the presence of 1 microM Cch was shifted to the right in parallel by nifedipine (1 microM). This was markedly potentiated by 60 mM K+ (the increase in ED50 of Ca2+ being 3 times at 6 mM and 15 times at 60 mM K+). No tension was evoked by Ca2+ up to 2.5 mM in 60 mM K+ solution containing 1 microM nifedipine but no Cch. 4. In the absence of nifedipine, Cch-induced contractions were potentiated by 60 mM K+, whereas in the presence of nifedipine, Cch-induced contractions were markedly inhibited by 60 mM K+. These mechanical changes were accompanied by an increase or a decrease in intracellular Ca2+. 5. A hypothesis is presented to explain the results which suggests that the kinetics of Ca2+ influx though a single type of pathway is modulated by membrane potential and receptor activation and that the susceptibility of the pathway to dihydropyridine blockade is closely related to the Ca2+ influx kinetics with receptor activation reducing and membrane depolarization increasing the susceptibility.
Takemoto
M
M
Second Department of Internal Medicine, School of Medicine, Nagoya University, Japan.
Ito
Y
Y
Takagi
K
K
Ogino
K
K
Tomita
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D004338:Drug Combinations; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
D002121:Calcium Channel Blockers; D004338:Drug Combinations; D002217:Carbachol; D009529:Nicardipine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium