Cardiac_and_Smooth Muscle.pdf

CARDIAC AND SMOOTH MUSCLE Roger Cameron, Ph.D. Department of Physiology [email protected] 444-7728 1 Cardiac muscle: where is it found? • Recall… skeletal muscle – bones and joints – GI tract: tongue, upper esophagus, anus • Cardiac: exclusively heart – Motility function: contraction of...

CARDIAC AND SMOOTH MUSCLE Roger Cameron, Ph.D. Department of Physiology [email protected] 444-7728 1 Cardiac muscle: where is it found? • Recall… skeletal muscle – bones and joints – GI tract: tongue, upper esophagus, anus • Cardiac: exclusively heart – Motility function: contraction of atria, ventricles, closing of valves – Conduction of electrical activity: pacing in SA node, through atria, ultimately to ventricles 2 Cardiac: cellular structure • Recall… skeletal – large multinucleated cells, arise from… – fusion of myoblasts – no gap junctions • Cardiac: individual cells – mononucleated – branching strands • Intercalated disks – contain gap junctions – heart is a syncytium nuclei of 2 myocytes intercalated disks between adjacent cells 3 Cardiac ultrastructure similar to skeletal • Sarcomeres: 3:1 actin-to-myosin ratio • SR, but less than skeletal • t-tubules, wider than skeletal • lots of mitochondria • oxidative metabolism ONLY (no capacity for glycolysis) 4 Excitation-Contraction Coupling Contraction • • Ca2+ : 0.1 M  2.0 M Ca2+ induced Ca2+ release Relaxation Positive Inotropy • Increase in extracellular Ca2+ •Catecholamines •Cardiac Glycosides Negative Inotropy 5 Cardiac action potentials • Recall… skeletal – Na+/K+ AP – brief: few ms • Cardiac – >10 different voltagegated channels – much longer (>300 ms) – Ca++ channels too! – different in different regions of heart 6 Recall… skeletal muscle contraction: twitches sum producing tetanus 7 Cardiac contraction coincident with AP • Heart contracts during AP—not after a latency like in skeletal muscle • Cardiac muscle cannot be tetanized—i.e., cannot exhibit sustained contraction 8 Recall… skeletal innervation/hormone response • -motor neurons (somatic motor nervous system) • Contraction neurogenic—skeletal muscle does NOT contract on its own • Insensitive to hormones on a short-time basis, but… • Long term (weeks/months) growth affected by anabolic/sex hormones (e.g., testosterone) 9 Cardiac muscle innervation/hormone response • Dual innervation by autonomic nervous system (ANS) – Parasympathetic: muscarinic ACh receptors slows heart rate (can stop heart) – Sympathetic: 1 norepinephrine receptors • Increase heart rate • Increase force of contraction • Sensitive to hormones: epinephrine (adrenalin) increases rate and contraction force • Contraction is myogenic—denervated heart contracts on its own – Inherent rate about 140 beats/min – continual parasympathetic (ACh) activity keeps rate at normal (reduced) levels (70 beats/min) 10 Cardiac length-tension relationship • Recall… narrow skeletal length/tension curve skeletal muscle • Cardiac much wider • operate on ascending phase • curve elevated by force norepinephrine and/or epinephrine sarcomere length 11 Smooth Muscle 12 Where found? Organs NOT under voluntary control • GI tract: surrounds lumen of esophagus, stomach, intestines, gallbladder, colon (GI motility) • Vascular: sphincters around arterioles (control blood flow); in walls of veins (change veins from bags to pipes) • Pulmonary: around airways in lung (control air flow) • Skin: causes piloerection (hair standing up) • Urinary tract: urinary bladder, urethral sphincters (micturition) • Reproductive system: ejaculation (♂), uterine contractions (♀) • Other places… 13 Cellular structure • Small distinct cells • mononucleated • elongated “football” shape • Diagram of intestinal smooth muscle: – longitudinal (outer) layer alters length of lumen – radial (inner) layer (cross section) alters diameter of lumen 14 Cellular ultrastructure • No sarcomeres, no t-tubules, rarefied SR • Actin-to-myosin ratio: >10:1 • Dense bodies tether thin filaments (like Z-disk) • Intermediate filaments tether dense bodies to membrane (“dense area”) • Cells physically connected to one another via mechanical junctions • Gap junctions often present; mediate cell-to-cell electrical communication 15 Relaxed vs contracted smooth muscle Contraction in all dimensions as opposed to linear contraction in skeletal/cardiac. 16 Multiunit vs single unit smooth muscle Multiunit: cells act independently (few gap junctions) Single unit: cells contract together (many gap junctions) Note innervation: axon varicosities containing synaptic vesicles. 17 EC coupling • No troponin, no tropomyosin • Ca++ from outside, some from SR • Ca++ binds to calmodulin (homology to troponin) • Activates myosin lightchain kinase (MLCK) • Phosphorylates myosin head group (light-chain region) 18 Crossbridge cycling (myosin ATPase activity) only when myosin in phosphated state • Relaxation requires two things: – cessation of stimulus: Ca++ (e.g., Ca++ pump)  Ca++-calmodulin  active MLCK – dephosphorylation of myosin via phosphatase activity: phosphatase myosin-Pi myosin Pi • Myosin phosphatase activity always present (constituitive), but activited MLCK (regulated by Ca++) is a faster reaction. 19 What leads to force development? • Ca++ APs (upper) produce force (lower) • “Slow waves” plus Ca++ APs produce force • Slow changes in Vm alone correlate with force • Agents (e.g.,hormones) alter force via changes in SR Ca++ release 20 21 Hyperpolarization-Mediated Vasodilation 22 cAMP Mediated Vasodilation 23 Nitric Oxide 24 Final Comments… • Extremely wide length-tension relationship—necessary to accommodate large vs small luminal volumes • Contraction principally myogenic via pacemakers; nervous system alters rate/strength of contraction • Dual innervation (like in heart) via the ANS – if parasympathetic stimulates, sympathetic usually (not always) inhibits – and vice versa • Smooth muscle sensitive to numerous extracellular chemical agents – hormones released into the blood (endocrine system) – agents released locally from other cells (paracrines) – especially important in GI motility 25