Phorbol ester-induced contractions of swine carotid artery are supported by slowly cycling crossbridges which are not dependent on calcium or myosin light chain phosphorylation.
This study determined if phorbol ester-induced contraction of vascular smooth muscle requires calcium-dependent myosin light chain (MLC) phosphorylation and, if not, whether the mechanical characteristics of the contraction in terms of stiffness and crossbridge cycling are similar to those during a calcium- and MLC phosphorylation-dependent contraction. Carotid arterial strips were exposed to 1.0 microM phorbol 12,13-dibutyrate (PDBu) in the presence of normal physiological salt solution (PSS) or after calcium depletion in calcium-free PSS and compared with contraction elicited by calcium-containing 110 mM KCl-PSS. PDBu induced maximal stress in both the presence and absence of calcium. While there was a temporal correlation between MLC phosphorylation and shortening velocity during KCl depolarization, shortening velocity was dissociated from MLC phosphorylation during PDBu stimulation. The stress-stiffness relationship was not different during KCl and PDBu stimulation, suggesting similar crossbridge interactions even though MLC phosphorylation levels were significantly different. These results demonstrate that PDBu-induced contraction of the swine carotid artery is not dependent on calcium or MLC phosphorylation. We suggest the possibility that activation of a calcium-independent PKC isoform may result in the expression of an inherent level of actin-activated myosin ATPase activity resulting in the slow development of stress.
Fulginiti
J
J
Bockus Research Institute, Graduate Hospital, Philadelphia, PA.
Singer
H A
HA
Moreland
R S
RS
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine
D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D009218:Myosins; D002118:Calcium