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General Shape of a Smooth Muscle Cell high S/V no obvious banding nucleus knp Smooth Muscle Motor Units? Contraction Patterns in Smooth Muscles Force 0 time knp Phasic (quick, SkMus-like) and tonic contractions Force Skeletal Muscle Twitch Smooth Muscle Twitch (can be shorter or longer) knp Time EC Coupling in Smooth Muscle Force Em Time Force tonus level hyperpolarized Em Time knp add one drug here Force Em add another type of drug here "normal" tonus roughly constant Em knp time Thin and Thick Filament Arrangements in Smooth Muscle Caldesmon Caldesmon In Relaxed Fibers Regulation of Smooth Muscle Contraction Thick Filament Regulation (on myosin light chain): -- Modulation by MLCK/MLCP -- Other Mechanisms Thin Filament Regulation (?): -- Does caldesmon have a regulatory role? -- Other mechanisms Calcium and the Control of MLCK Leading to Control of the Myosin Light Chain Ca++ + Calmodulin Calmodulin-- Ca ++ MLCK ATP + Myosin * ADP * Pi MLCK -Calmodulin -Ca++ MLCK -Calmodulin -Ca ++ P--Myosin * ADP * Pi + ADP Contracted SM Mus There’s always a reverse process: P--Myosin --Actin MLCP (Phosphatase) Myosin --Actin + Pi MLCP phosphatase is inhibited by a Ca++ dependent pathway (but in any case, its maximum activity is lower than MLCK) SM Contraction and Relaxation: Ca++ and the Regulation of Phosphorylation of the Myosin Light Chain MLCK (inactive) add Ca ++ (from plasma membrane) Calmodulin Calmodulin Ca++ ATP remove Ca ++ (via plasma membrane) MLCK-- Calmodulin -- Ca ++ Myosin (after a diagram in Berne and Levy, Physiology , Mosby, 1983) ADP Myosin-Pi Pi MLCP Phosphorylated Crossbridge Regulation via the PKC Pathway Latch Mechanism?