PHYL3001 Lecture Notes - Lecture 8: Phosphatidylinositol, Inositol Trisphosphate Receptor, Cyclic Adenosine Monophosphate
LECTURE EIGHT: Excitation Contraction Coupling
VOC and Electromechanical Coupling:
• Single unit
o Show AP
o Caused opening L-type Ca2+ channels
o Ca2+ brought in from outside → binds to calmodulin → triggers
contraction
o Delayed opening of Kv channels → delayed rectifier channels
• Multi unit
o Do not show action potentials
o L-type voltage gated Ca2+ channels → same mechanisms as single
unit
o Kv channels open as L-type channels do → AP not generated
o High Ca concentration causes K to leave cell
• Depolarization opens voltage gated calcium channels/voltage operated
channels (VOC)
• Calcium influx through L-type OC increases intracellular calcium
• Rise in intracellular calcium produces contraction
• Contraction triggered through VOC opening and membrane potential
changes → electromechanical coupling
Smooth Muscle P2X Receptors:
• ATP stimulates P2X receptors
• Non selective cation channel
• Na and Ca enter → depolarization opens L-type Ca channels
• P2X → only true ligand gated ion channel in SM that responds to
extracellular signals
ACh ROC:
• Causes depolarization
• Produces inward currents in most SM
• Channel is a non selective cation channel
• Molecular nature of channel unconfirmed
• Suggested to be a member of the transient receptor potential (TRP)
family of cation channels
• Channel is not the agonist receptor
• Mechanism of ROC activation by M-cholingeric (or a-adrenergic)
receptors unknown
• Gi/Go G-proteins may be required
Electromechanical Coupling ROCs:
• ACh binds to M receptor on calmodulin
• G-protein binds to ROC
• Non selective ion channel → Ca and N in, K out
• By itself causes depolarization because positive current going in →
dominant Na inward current
• Opens L-type channels → allows Ca to enter through L-type channels
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Document Summary
Smooth muscle p2x receptors: atp stimulates p2x receptors, non selective cation channel, na and ca enter depolarization opens l-type ca channels, p2x only true ligand gated ion channel in sm that responds to extracellular signals. Activates camp: g protein activated binds gtp, dissociates from g protein and binds to membrane bound enzyme. Gq type signaling: m1, m3, m5 or a-adrenergic receptors activated by ach or na, activates gq activates phospholipase c, phosphatidylinositol broken down into the second messengers inositol triphosphate and diacylglycerol form protein kinase c (pkc) Ip3 binds to ip3 receptor ligand gated ca ion channel on sr membrane: no change in membrane potential. Pharmacomechanical coupling excitation: activation of calcium release and contraction without a change in membrane potential, some calcium entry through roc, calcium is released from intracellular stores, gq activation produces ip3 that opens ip3 sensitive calcium channels on. Intracellular store is the sarcoplasmic reticulum (sr) the sr.
