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Physiology 121, Lecture 8 Smooth Muscle Contraction (Dr. Donald B. Thomason) Objectives: The student should be able to: 1. Match the phases of shortening (isometric and isotonic) with the tension developed during these phases. 2. State the difference between syncytial and multi-unit smooth muscle. 3. State the electrical conditions that modulate smooth muscle contraction. 4. Name the type of innervation characteristic of smooth muscle. 5. List the key proteins that regulate smooth muscle contraction. 6. List the two ways to produce more force by smooth muscle. Outline: I. The Diversity of Smooth Muscle Function Diversity of Smooth Muscle Function Examples: regulation of vascular resistance and blood flow propulsion and compartmentalization of the digestive system pilomotor function optics of vision II. Organization of Smooth Muscle Smooth Muscle Cell Types A. Smooth muscle cells are primarily mononuclear Syncytial or Unitary Autonomic Nerve B. Smooth muscles are mechanically and electrically diverse Autonomic Nerve Multi-unit 1. Syncytial or “single-unit” smooth muscle 2. Multi-unit smooth muscle C Smooth muscle cells do not normally exhibit well-structured sarcomeres Muscle Fiber Organization Striated Muscle Smooth Muscle III. Contractile Activity and its Regulation A. The action potential and ion fluxes in smooth muscle 1. Membrane conductances are different from skeletal muscle 2. Calcium currents can play an important role IK membrane current membrane potential (mV) Smooth Muscle Action Potential 0 -50 0 100 200 I Na 100 200 time (msec) IK membrane current membrane potential (mV) Smooth Muscle Action Potential 0 -50 0 I Na 100 200 time (msec) I Ca 3. An action potential need not occur for contraction tension potential (mV) potential (mV) tension Smooth Muscle Contraction 0 -50 0 1 2 time (sec) 0 -50 0 1 2 time (sec) 4. Pacemaker activity causes spontaneous contraction potential (mV) tension Smooth Muscle Pacemaker Activity 0 -50 0 1 2 time (sec) 3 B. Nervous control of smooth muscle contraction 1. Innervation is exclusively autonomic 2. Modulation of contractile activation by nerves a. excitatory effects b. inhibitory effects Neurotransmitter Effects Substance ACh Effect Excitatory Mechanism depolarization g Inhibitory Example Na g Ca hyperpolarization gK NE Excitatory depolarization g Inhibitory Ca g Na gK increased peristalsis coronary vasodilation vasoconstriction g Cl hyperpolarization g pacemaker K E-C coupling decreased peristalsis (human) C. Non-neural control of smooth muscle contraction 1. Local and distant activation 2. Receptor-mediated and non-receptor mediated mechanisms Local and Distant Activation Hormones e.g., cholesystokinin, estrogen, PDGF, oxytocin Metabolites e.g., H+, CO2 , adenosine IV. Mechanism of Contraction of Smooth Muscle A. Calcium and the permissive effect of myosin light chain-phosphorylation 1. Calcium-calmodulin interaction 2. Myosin light-chain kinase 3. Cross-bridge cycling Smooth Muscle Contractile Mechanism Ca intracellular stores Ca 2+ 2+ receptor-activated potential sensitive + CM CM-Ca 2+ + MLCK actin + myosin -P contraction myosin + ATP phosphatase Pi B. The central role of calcium and its various sources α-Adrenoreceptor-mediated Vasoconstriction Ca 2+ Ca α2 2+ α1 G G Ca 2+ G Ca inhibitors: nifedipine pertussis toxin PLC 2+ IP3 C. Phosphatase activity and the cessation of cross-bridge cycling Factors Which Regulate Smooth Muscle Contraction Velocity : Activation of MLCK/phosphatase Magnitude : 1. frequency of stimulation 2. number of cells stimulated PIP2 D. The latch mechanism E. The stress-relaxation mechanism Stretch-Relaxation Phenomenon Length Force time Length Force