Types of Smooth MuscleHow the cells behaveLeft: Single unitBlood vessels (vasodilation and constriction), intestine (motility), full term uterus (contractions)Coupled by gap junctions (electrical and metabolic)Excitation spreads through gap junctions- whole thing behaves as a unitVaricosities releasing transmitterRight: Multi-UnitEye (iris (pupil), ciliary body-change shape of lens (accommodation)) non pregnant uterusCells are individual not coupled by gap junctionsEach cell responds individuallySome smooth muscle doesn’t receive any innervations- Single unitCyclically active (intrinsically active)Cardiac and pacemaker cells- periodic action potentialsSubject to hormone and paracrine control as is all smooth muscleHistamine= inflammationNitric Oxide= synthesized by endothelial cells and causes relaxation of blood vesselsMost do receive innervationsBladder is stretch sensitiveVascular smooth muscle is also stretch sensitive- maintenance of blood pressureRegulation of [Ca2+]i in smooth muscle cellsTrigger for contractionWhere does calcium come fromCenter is calciumAlong periphery are mechanism for Calcium to come inUpper leftCa2+ channel coupled to receptor for hormone or neurotransmitterCa2+ moves inwardly down electrochemical gradientRight1. Ca2+ channels that are voltage gated2. Stretch activated mechanically gated ca2+ channels3. Open in response to depletion in Ca2+* There are also voltage gated Na+ channels in right to amplify depolarization – not usually an all or none action potential but is enough to open the Ca2+ channelsMost don’t have action potential in smooth cells, but you can have regenerative responses just not all or noneAlso have K+ channels to dampen the excitability of the cellCa2+ channels in the plasma membrane are the most important for triggering contraction in the MULTIUNIT cellsThere are always Na+/K+ pumps because they are highly electrogenicLower leftBinding of ligand to receptor that’s coupled to PLC and generates IP3 that generates release of Ca2+ from ERThis is the most important for single unit systemsLower rightWhere the Ca2+ goes1. Removed by calcium ATPases2. or by the Na+/Ca2+ antiportone calcium out for every 3 sodium it lets in3. Or sequestration of Ca2+ back into the ERNewly Described plasma membrane Ca2+ channelsMore realistic diagram of previous slideLeft side: IP3 system coupled via G protein to PLC which produces the IP3 which causes release of Ca2+ from ER. This IP3 receptor in the ER membrane is an IP3 gated cation channel (Ca2+). Well known mechanismThis paper also shows that there are a small number of IP3 gated cation channels in the plasma membrane which can let in Ca2+ from outside. There are not very many of these receptors in membrane but they have capacitance for Ca2+ to come through. These channels can carry large calcium current and let a lot in.Time course different: ER releases Ca2+ rapidly but the plasma membrane channels are much slower but stay active for longer.New Ca2+ channel in membrane: pink. Many copies but low conductance of calcium. Important because this is the molecular basis for store operated calcium entry (when cell is depleted of calcium). First to show this mechanism.STIM1 is an ER membrane protein that normally when Ca2+ levels in the ER are high the STIM1 proteins are scattered through membrane but if Ca2+ levels are low in the ER then the STIM1 proteins aggregate in the membrane. In this state, the cytoplasmic side of this protein can bind to the OR1 calcium channel and that opens that channel.Shows that the regulation of Ca2+ is complicated (multiple pathways)Crossbridge cycling in smooth muscleActin and myosin in smooth muscleCrossbridges form between these two, there’s less of it so the force is much less than skeletal muscleThe time course is way slower and longer than skeletal muscleThis slide shows mechanismThick filament and actin of thin filament and crossbridge of myosin moleculeDotted outline partCa2+ turns this on (bound to calmodulin and when Ca2+ binds it activates a kinase and the substrate of this kinase is myosin) Light chain forms head of myosin molecule. Phosphorylates head of the myosin which is important because crossbirdge cycling in smooth muscle requires phosphorylation of the myosin head. Like a switch. Faster cycling because it is faster than slow cycling but it is slow. Faster cycling corresponds to the 6 step cycle from before. When myosin head is phosphorylated it can cycle through those six steps (this generates the force)The phosphorylation of the myosin head to make this possible requires one ATPHow do you turn it off?Dephosphorylation of myosin headSpecific myosin light chain phosphtase and the contraction is turned offThere is regulation of the mechanismPart that isn’t dottedThe preferred substrate of the phosphatase is the unattached myosin headHas some activity to deattach the attached myosin head however but with much less activityOn left: attached but dephosphorylated myosin crossbridgeMost of the product will be up in left cornerSome small percentage of the cross bridges get in the state in the lower left corner (called catch state) because gets caught in this state. The force gets built upallows SMOOTH MUSCLE TO MAINTAIN FORCE FOR LONG TIMELeaves this state by phosphorylating myosin head goes back to fast cyclingOr can detach by binding ATP. But ATP binding affinity of attached myosin head very low so usually the catch state is long.Some invertebrates have similar mechanismsClams clamp down very tightly for long times involves this catch stateIntroduction to Endocrine PhysiologyThings to Remember1. Names, locations, secretions of major endocrine organs (Fig 7-2)2. General properties of peptide, steroid and amine hormones (Table 7-1)3. Synthesis, storage and processing of peptides (Fig 7-3)4. Synthesis and action of steroid hormones (Figs 7-6 and 7-7)5. Tyrosinecatecholamines and thyroid hormones (Fig 7-8)6. Hormones of the posterior pituitary (Fig 7-12) and anterior pituitaryNegative Feedback in hypothalamic- anterior pituitary systemsHypothalamus contains purple neurons that release hormones into the capillariesStimulating growthCan see the negative feedbackThe tropic hormone inhibits the releasing hormoneBISC 307L 1st Edition Lecture 13 Current Lecture- Types of Smooth Muscleoo How the cells behaveo Left: Single unit Blood vessels (vasodilation and constriction), intestine (motility), full term uterus (contractions) Coupled by