Smooth Muscle Physiology PDF

PHYL2002: Physiology of Cells Smooth Muscle Dr Peter McFawn 2023  Aims Define, smooth muscle, phasic muscle, tonic muscle, multi-unit muscle, single-unit muscle and L-type channel. Describe the structure of smooth muscle including how...

PHYL2002: Physiology of Cells Smooth Muscle Dr Peter McFawn 2023  Aims Define, smooth muscle, phasic muscle, tonic muscle, multi-unit muscle, single-unit muscle and L-type channel. Describe the structure of smooth muscle including how it is linked to other cells and the equivalent of sarcomeres in SM. Explain how slow wave spread from the ICC to SM and cause action potentials in gastro-intestinal SM Describe action potentials in gut SM including the ionic movements and channels Describe how excitation contraction coupling occurs in gut smooth muscle Explain the role of calmodulin, myosin light chain kinase and myosin light chain phosphatase in contraction of SM List the effect and receptor for acetylcholine (ACh) and noradrenalin (NA) in gut, blood vessel and airway smooth muscle  Outline Structure of Smooth Muscle Phasic and Tonic Smooth Muscle Pacemaker activity and slow waves Action potentials in smooth muscle Excitation contraction coupling  Kinds of Muscle Sherwood 9th Ed Ch 8  Smooth Muscle Sherwood 2nd ed ch 8 Structure Cytoskeleton Thick Filaments (Myosin) Thin Filaments (Actin) Dense bodies Sherwood 2nd ed ch 8 Vascular Smooth Muscle Sherwood 2nd ed ch 10 Airway Smooth Muscle  Smooth (visceral) Muscle Not striated Smooth muscle found in: − Blood vessels. − Respiratory system − Alimentary tract − Bladder − Uterus Controlled by Autonomic nerves, hormones, local mediators.  Smooth (visceral) Muscle Contractions are slow Very resistant to fatigue Contraction used little energy Tone can be maintained indefinably Some smooth muscle are phasic i.e. they show rhythmic contractions.  Multi Unit Smooth Muscle Discreet motor units (like skeletal muscle) Units must be activated separately Always produced smooth tonic contractions when activated. Not rhythmic Found in eye, Large blood vessels, Airways  Single Unit Smooth Muscle Cells function as a single unit (like Heart) Gap junctions between cells Tonic in Bladder, small blood vessels. Phasic (rhythmic) in Gut, Uterus Often show slow waves or basal electrical rhythm Rhythmicity in Smooth Muscle Cardiac Pacemaker Gut Pacemaker  Gut Smooth Muscle Sherwood 2nd ed ch 16  Interstitial Cells of Cajal (ICC) Gastric and intestinal smooth muscle is electromechanically coupled Interstitial cells of Cajal are the pacemaker cells which trigger depolarisation  Gap Junctions Sherwood 2nd ed ch 8 Pacemaker potential travels cell to cell from ICC to SM Connections by gap junctions Sherwood 6th ed Ch 3 Pores between cells formed by connexon allow passage of ions  Smooth Muscle Action Potential Rest Depolarisation Kv Kir Kv Kir Low [Ca2+]i K+ K+ Calmodulin High [Ca2+]i Ca2+ Ca2+ L-type L-type  Smooth Muscle Action Potential Rest Repolarisation Kv Kir Kv Kir Low [Ca2+]i K+ K+ Calmodulin High [Ca2+]i Ca2+ Ca2+ L-type L-type  Phasic Smooth Muscle Interstitial Cells of Cajal generate pacemaker potentials “slow waves” Slow waves last second and ~10-15mV Pass to muscle through gap juntions Action potential due to opening of voltage gated calcium channels (L-type channel) Repolarization from opening Kv channels Resting potential from open Kir channels  Excitation Contraction Coupling MLCP Actin pMyosin Myosin MLCK Contraction Calmodulin Ca2+ Alan Mak Dep Biochem Queen’s University Ontario  Excitation Contraction Coupling MLCP Actin pMyosin Myosin MLCK Contraction CalM-Ca2+ Alan Mak Dep Biochem Queen’s Uni Ontario  Smooth Muscle Contraction Contraction produced by Actin and Myosin Rise in intracellular Ca2+ is the trigger for contraction Calcium binds Calmodulin Ca2+-Calmodulin activates Myosin light chain kinase (MLCK). Myosin is phosphorylated and binds actin Contraction occurs Dephosphorylation by myosin light chain phosphatase (MLCP)  Smooth Muscle Contraction Some smooth muscles use intracellular calcium stores (e.g. airways, blood vessels) Some smooth muscles rely on extracellular calcium (e.g. gut) Calcium influx can be triggered by action potentials (e.g. gut) Calcium influx can be triggered by receptor binding (e.g. blood vessels and adrenaline)  Neural Control Tissue Acetylcholine Noradrenalin Blood vessels Relax, vis nitric oxide Constrict, a-adrenergic Airways Constrict, M-cholinergic Relax, b-adrenergic Gut Constrict, M-cholinergic Relax, b-adrenergic Gut sphincters Relax, vis nitric oxide Constrict, a-adrenergic Acetylcholine (ACh) acting on muscarinic (M) receptors always constricts smooth muscle ACh induced relaxation from a second transmitter, nitric oxide. a-adrenergic receptors typically constrict b-adrenergic receptors mostly relax Need to know about G-protein coupled receptors (GPCR)  Summary Three kinds of muscle Smooth muscle has no visible sarcomeres Contraction is still via actin and myosin Control of contraction is from Ca2+ binding to calmodulin and phosphorylation of myosin by MLCK. Tonic muscle produces constant contraction (blood vessels), phasic muscle shows rhythmic contraction (gut) Slow waves in gut generated by ICC depolarize smooth muscle causing contraction Gut muscle contraction triggered by opening L-type calcium channels, direct calcium entry ACh mostly causes contraction but can relax via a second transmitter. NA relaxes via b-receptors and stimulates via a- receptors