Effects of dihydropyridines on stress, myosin phosphorylation, and V0 in smooth muscle.
Contraction of swine carotid medial fibers with KCl results in stress development associated with high levels of myosin light chain (MLC) phosphorylation and maximum shortening velocity (V0) indicative of rapidly cycling phosphorylated cross bridges. The period of stress maintenance is characterized by low levels of MLC phosphorylation and V0; the maintained stress is postulated to be supported by dephosphorylated, slowly cycling cross bridges (latch bridges). This study was designed to examine the roles of calcium in both stress development and stress maintenance. Medial strips were contracted with 110 mM KCl in the presence of varying concentrations of the calcium channel blocker nifedipine (1-100 nM) or were contracted with varying concentrations of the calcium channel activator BAY-K 8644 (0.3-3 microM). Nifedipine significantly depressed stress maintenance and V0, but had little effect on either stress development or MLC phosphorylation. Conversely, BAY-K 8644 produced contractions that were equal to those elicited with 110 mM KCl but that were characterized by low levels of V0 and basal or low levels of MLC phosphorylation. These data suggest that the mechanisms by which the cellular calcium concentration increases and the limitations on this increase may impact differently on different regulatory processes of contraction and, thereby, on cross bridge behavior.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine
D002121:Calcium Channel Blockers; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009218:Myosins; D009543:Nifedipine; D002118:Calcium