Published on February 7, 2008
SMOOTH MUSCLE PHYSIOLOGY: SMOOTH MUSCLE PHYSIOLOGY General Lecture Goal: : General Lecture Goal: To describe the unique features of smooth muscle in comparison to striated muscle. Special emphasis on control of contractile activation. I. STRUCTURAL CHARACTERISTICS OF SMOOTH MUSCLE.: I. STRUCTURAL CHARACTERISTICS OF SMOOTH MUSCLE. Smooth Muscle Size and Shape: Smooth Muscle Size and Shape Spindle shaped cells Relatively small compared to skeletal and cardiac muscle 2-5 mm wide 50-200 mm long. Contractile Apparatus: Contractile Apparatus No sarcomeres (hence the name smooth). myosin (thick filament). actin (thin-filament) Lack neat hexagonal arrangement of actin and myosin Actin/myosin ratio: greater in smooth muscle (10:1) than in skeletal muscle (2:1). Figure 1. Smooth Muscle Architecture: Figure 1. Smooth Muscle Architecture Intermediate filaments: Intermediate filaments Cytoskeletal elements which form a structural backbone against which contraction occurs. Desmin and vimentin are 2 protein components of this cytoskeleton. Dense bodies: Dense bodies Serve as anchors for the thin-filament protein actin. Analogous to z-lines in striated muscle Contain the protein actinin Dense zones. Mechanical junctions also attach adjacent smooth muscle cells. Gap Junctions: Gap Junctions Allow direct electrical communications between adjacent smooth muscle cells Gap junction density varies from tissue to tissue. No T-tubules and no terminal cistern system.: No T-tubules and no terminal cistern system. Small size of smooth muscle Smooth muscle does not require action potential to contract. Poorly developed sarcoplasmic reticulum.: Poorly developed sarcoplasmic reticulum. Needs extracellular Ca++ source for contraction Compare: cardiac muscle (partial-dependence) skeletal muscle (negligible-dependence). Tropomyosin-Tropomyosin Complex: Tropomyosin-Tropomyosin Complex Tropomyosin present in smooth muscle actin but: Exact functional role, if any, unclear. No troponin present at all Therefore, Troponin-I does not inhibit cross-bridge cycling in smooth muscle. Figure 2. The Structure of Myosin.: Figure 2. The Structure of Myosin. Myosin Light Chains: Myosin Light Chains Play a key regulatory role in smooth muscle. Don’t confuse “light chains of myosin” with the term "light meromyosin" II. CLASSIFICATION OF SMOOTH MUSCLE: II. CLASSIFICATION OF SMOOTH MUSCLE SINGLE UNIT (VISCERAL) AND MULTIUNIT SUBTYPES. Smooth Muscle Innervation: Smooth Muscle Innervation Innervated by the autonomic nervous system. Nerve varicosities are usually some distance from the muscle No specialized nerve-muscle junction. Spectrum of Smooth Muscle Types: Spectrum of Smooth Muscle Types “Single” and “Multiunit” represent extremes of a spectrum. Single Unit Smooth Muscle.: Single Unit Smooth Muscle. Also called unitary or visceral smooth muscle. Behaves in a syncytial manner. Single unit smooth muscle: Tends to have many gap junctions between cells. Relatively sparse innervation Organs with Single Unit Muscle include:: Organs with Single Unit Muscle include: Figure 3: Single Unit Smooth Muscle: Figure 3: Single Unit Smooth Muscle Electrical Characteristics:Single Unit Smooth Muscle: Electrical Characteristics: Single Unit Smooth Muscle Slow Wave Potentials: Sometimes cause contractions; sometimes do not. Action potentials (all or none) spikes. Almost always an associated contraction. Mechanical Characteristics: Single Unit Smooth Muscle: Mechanical Characteristics: Single Unit Smooth Muscle Plasticity. (also called “stress relaxation”) Slow stretch --> lengthening e.g. bladder capacity w/o pressure increase Stretch induced contraction. Fast stretch causes depolarization and leads to contraction Multiunit Smooth Muscle Organs.: Multiunit Smooth Muscle Organs. Each smooth muscle cell acts independently (like skeletal muscle). Less gap junctions between cells Higher innervation ratios than visceral smooth muscle. Multiunit smooth muscle organs include:: Multiunit smooth muscle organs include: Figure 4: Multiunit Smooth Muscle: Figure 4: Multiunit Smooth Muscle Electrical Characteristics: Multiunit Smooth Muscle: Electrical Characteristics: Multiunit Smooth Muscle Membrane potential of multiunit smooth muscle is stable Typically, do not display action potentials when stimulated to contract. Mechanical Characteristics: Multiunit Smooth Muscle: Mechanical Characteristics: Multiunit Smooth Muscle Tone: Constant and stable low level of contraction Examples. Blood vessels and GI sphincters. Tone is intrinsic property -- does not depend on nerves Tone may be modified by: nerves hormones drugs Hormonal Modification of Smooth Muscle Type.: Hormonal Modification of Smooth Muscle Type. High progesterone during pregancy Reduce number of gap junctions in myometrial smooth muscle Myometrium behaves more like non-innervated multiunit smooth muscle Uterus remains relatively quiescent. Hormonal Modification of Smooth Muscle Type.: Hormonal Modification of Smooth Muscle Type. Rising estrogen levels at term: Cause smooth muscle hypertrophy Increase the number of gap junctions. Myometrial smooth muscle behaves more as a single unit Contributes significantly to parturition! III. Actin-Myosin Interactions are Controlled Differently in Smooth Muscle than Striated Muscle: III. Actin-Myosin Interactions are Controlled Differently in Smooth Muscle than Striated Muscle Figure 5: Smooth Muscle Control: Figure 5: Smooth Muscle Control Summary of Smooth Muscle Control: Summary of Smooth Muscle Control High [Ca++]i triggers contraction Ca-calmodulin-MLCK phosphorylates myosin Low intracellular calcium is associated with relaxation Control Differs from Striated Muscle: myosin-based not Actin-troposmysosin-troponin complex-based. High MLCK/MLCP Activity Ratio -->Contraction: High MLCK/MLCP Activity Ratio -->Contraction High Ca++ causes contaction by increasing MLCK activity High cAMP causes relaxation by effectively lowering [MLCK] ? Control by altering MLCP activity Increased Phosphatase C activity --> relaxation Decrased Phosphatase C activity --> contraction Fast Cross-Bridge Cycling is Similar to Striated Muscle.: Fast Cross-Bridge Cycling is Similar to Striated Muscle. ATP binds to the myosin head Provides energy to release myosin from actin Provides energy to re-cock myosin head. Myosin head spontaneously attaches at a new actin site Power stroke: Occurs with the shedding of ADP-P from the previous cycle Minimum Condition for Smooth Muscle Contraction: Minimum Condition for Smooth Muscle Contraction Phosphorylation of myosin light chains ATP is needed: to phosphorlate myosin light chains to support fast cross-bridge cycling Multiple cross bridge cycles, each with an ATP hydrolysis, follow a single myosin light chain phosphorylation. Smooth Muscle Latch State.: Smooth Muscle Latch State. Efficiency is low ATP required for control (light chain phosphorylation) ATP required for cross bridge cycling. Economy is high: Absence of shortening: maintain tone (force) with minimal expenditure of ATP. Called “latch state”. Figure 6: Smooth Muscle Latch States: Figure 6: Smooth Muscle Latch States Relaxation of Smooth Muscle: Relaxation of Smooth Muscle Low intracellular [Ca++]. Calcium extrusion from the cell 3Na+/Ca++ exchanger Sarcolemmal Ca++ATPase Reuptake by the sarcoplasmic reticulum SR Ca++ ATPase. IV. SIGNALING OF CONTRACTION IN SMOOTH MUSCLE.: IV. SIGNALING OF CONTRACTION IN SMOOTH MUSCLE. Resting Membrane Potential: Resting Membrane Potential Relatively positive (perhaps -55 mV) due to high Na+ leak. Inward Ca++ current Extracellular [Ca++] = 10-3 M Intraracellular [Ca++] = 10-7 M Contraction of Smooth Muscle: Contraction of Smooth Muscle Requires increased intracellular [Ca++]: Voltage-gated [Ca++] channels Action potential activated or Local-graded potential activated Ligand-gated [Ca++] channels Voltage-Gated Channels in Smooth Muscle. : Voltage-Gated Channels in Smooth Muscle. Smooth muscle has relatively few of the voltage-gated (fast) Na+ channels. Major depolarizing current carried by Ca++ channels L-type (long acting) T-type (transient) L-Type (Slow) Ca++ Channels. : L-Type (Slow) Ca++ Channels. Open slowly and close slowly. Affected by “Ca++-channel blockers”. Open at relatively positive Em. T-Type (Fast) Ca++ Channels.: T-Type (Fast) Ca++ Channels. Open and close quickly. Not blocked by Ca++ channel blockers. Rapid influx --> Ca++-induced Ca++ release from the SR. Potassium Channels in Smooth Muscle: Potassium Channels in Smooth Muscle Inward Rectifier K+-channel (IK1 or IKrec) Delayed-rectifier K+ channels (IK). Inward Rectifier K+-channel (IK1 or IKrec): Inward Rectifier K+-channel (IK1 or IKrec) Open at resting membrane potentials Cause the high basal membrane K+ permeability. Close quickly with membrane depolarization. Delayed-Rectifier K+ Channels (IK).: Delayed-Rectifier K+ Channels (IK). Open during depolarization: voltage-dependent fashion time-delayed fashion. Potassium efflux causes: Repolarization phase of action potentials Delayed hyperpolarization following large graded depolarizations. Hyperpolarization --> L-type Ca++ channel closure --> Relaxation Receptor-Operated Ion Channels: Receptor-Operated Ion Channels Secondarily opens or closes voltage-gated Ca++ channels to cause contraction or relaxation. Directly affect contactile machinery through second messengers Ligand-Operated G-Protein Dependent K-Channels.: Ligand-Operated G-Protein Dependent K-Channels. Muscarinic receptors and possibly by adenosine receptors. Potassium efflux hyperpolarizes the cell Slow L-type Ca++ channels close Muscle relaxation occurs. Ligand-Operated ATP-Sensitive K-Channels.: Ligand-Operated ATP-Sensitive K-Channels. Closed when [ATP]i normal. Opens in ischemia: K+ efflux --> hyperpolarization Ca++ channels close Intracellular Ca++ decreases Smooth muscle relaxes. Receptor Operated Second Messengers: Receptor Operated Second Messengers cAMP-Dependent Relaxation.: cAMP-Dependent Relaxation. b-adrenergic agonists, adenosine, PGI2 cAMP activates Protein kinase A (PKA) PKA phosphylates MLCK MLCK-P is Ca-calmodulin insensitive Relaxation results ? cAMP increases Ca++ reuptake by SR in some cells Phosphorylation of Phospholambam inhibits this inhibitor of SR Ca++ reuptake cGMP-Dependent Relaxation.: cGMP-Dependent Relaxation. NO, ANP --> Increased cGMP Activates cGMP-dependent protein kinase --> Decreased [Ca++]i Phosphorylation closes K+ channel Hyperpolarizes cell; Prevents Ca++ entry Decreased SR Reuptake Phosphorylation of Phospholambam inhibits this inhibitor of SR Ca++ reuptake Decreased SR Ca++ release Phosphorylation of IP3 receptor PLC-Dependent Contraction.: PLC-Dependent Contraction. AII, a1-adrenergic agonist, endothelin IP3 releases intracellular Ca++ stores. DAG activates PKC ? L-type Ca++ channel phosphorylation -- channels may open at more neg. voltage ? PKC may act as MLCK (phosphorylate myosin light chains). Questions?: Questions?
http://www.ursa.kcom.edu/Department/SlideSets/spring/SmMuscle/PPSmMuscle4.ppt Hematocrit changes during pregnancy http://www.rnceus.com/cbc/cbchct.html