1 / 25

Ion Channels in Smooth Muscle Tone Regulation

Explore the role of ion channels in regulating smooth muscle tone in various systems, such as vascular, bronchial, gastrointestinal, urinary, and uterine. Understand the mechanisms of ion channels and their impact on smooth muscle contraction and relaxation.

psiegel
Download Presentation

Ion Channels in Smooth Muscle Tone Regulation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Ion channels in the regulation of smooth muscle tone Dr. Janos Pataricza – Dr. Andras Toth Department of Pharmacology and Pharmacotherapy University of Szeged 28th of November, 2017

  2. Content • Regulation of smooth muscle contraction • Some important ion channels and the tone of the smooth muscle • K+ channels and vascular smooth muscle tone • Cl- channels and vascular smooth muscle tone -Possible relationships among voltage-dependent Ca2+channels, ryanodine-sensitive Ca2+- release (RyR) channels, large-conductance Ca2+-sensitive K+(BKCa) channels, and Ca2+-a activated Cl− (ClCa) channels to regulate smooth muscle contractility • Ion channels in bronchial smooth muscle cells • Involvement of ion channels in the regulation of cholinergic excitation in gastrointestinal tract • Ion channels in the urinary tract • Ion channels in the regulation of uterinal smooth muscle tone -Strech-activated TREK-1, a type of two-pore K+ channels (K2P) also regulates myometrial tone -Pregnancy, hypoxia and K+ ion channels -Subfamily members of voltage dependent K+ channels (Kv7 and Kv11) in the regulation of uterinal tone • Transient receptor potential channels (TRPC) in smooth muscle cells - link to intracellular signaling • A crosstalk between the plasma membrane and sarcoplasmic reticulum involving Ca2+ and K+ channels in smooth muscle cells -Surface coupling between junctional sarcoplasmic reticulum (SR) and plasma membrane: leaflets of SR and cell membranes are separated by an 12- to 20-nm gap -Possible mechanisms of action of PKA/PKG and PKC on Ca2+sparks, BKCa channels, and SR Ca2+-ATPase in arterial smooth muscle cells • Endothelial nitric oxide influence the tone through modulation of ion channels in smooth muscle cell of human umbilical artery • Some basic properties of ionic regulation of smooth muscle tone • Current research

  3. Principle of regulation of smooth muscle contraction/relaxation

  4. 2 principal pathways of regulation of smooth muscle contraction MLCK dependent MLCK independent

  5. Regulation of smooth muscle contraction Webb RC, Advan in Physiol Edu 2003;27:201-206

  6. Some important ion channels and vascular smooth muscle tone Jackson WF, Hypertension. 2000;35:173-178 Inward rectifier K+ channel (KIR) ATP-sensitive K+ channel, (KATP), voltage dependent K+ channel (KV), big conductance Ca2+ activated K+ channel (BKCa), store-operated Ca2+ channel (SOCC), stretch-activated K+ channel (SACC), sarcoplasmic reticulum ryanodine-sensitive Ca2+ channel (RyR)

  7. K+ channels and vascular smooth muscle tone Jackson WF, Hypertension. 2000;35:173-178

  8. Cl− channels and vascular smooth muscle tone Jackson WF, Hypertension. 2000;35:173-178

  9. Possible relationships among voltage-dependent Ca2+channels, ryanodine-sensitive Ca2+-release (RyR) channels, large-conductance Ca2+-sensitive K+(BKCa) channels, and Ca2+-activated Cl− (ClCa) channels to regulate smooth muscle contractility. JaggarJH et al., Am J Physiol Cell Physiol 2000;278:C235-C256 - +

  10. Ion channels in bronchial smooth muscle cells Perez-Zoghbi JF et al, Pulm Pharmacol Ther. 2009 ;22(5):388-97 Find: Receptor-operated Ca2+ influx or channels (ROC) Store-operated Ca2+ entry or channels (SOC) Ca2+-activated K+ channels (KCa1.1, KCa3.1) Voltage-dependent Ca2+ channels (VDC) Stretch-activated channels (SA) are directly gated by physical stimuli

  11. Involvement of ion channels in the regulation of cholinergic excitation in gastrointestinal tract Koh SD, Rhee PLJ Neurogastroenterol Motil. 2013;19(4):426-32. Possible post-junctional mechanisms responsible for cholinergic excitation. Acetylcholine (ACh) is coupled to Gq/11 protein and activates conductance(s) through inositol-1,4,5-triphosphate receptor (IP3R) in interstitial cells of Cajal (ICC) and smooth muscle cells (SMC). ACh might also be coupled to G12/13 protein and activate Rho-Kinase (RhoK) pathway to induce contraction in SMC. ER: endoplasmic reticulum; PLC: phospholipase C; DAG: diacyl glycerol; PKC: protein kinase C; CaCC: Ca2+-activated Cl- channels; NSCC: non-selective cation channels; GJ: gap junction; MLCP: myosine light chain phosphatase.

  12. Ion channels in the urinary tract Kyle BD,Channels (Austin). 2014;8(5):393-401 urinary bladder urethra KATP, ATP-sensitive K+ channel; BKCa, large conductance, Ca2+-activated K+ channel; Kv, voltage-gated K+ channel; K2P, 2-pore domain K+ channel; IKCa, intermediate conductance K+ channel; SKCa, small conductance K+ channel; VGCC, voltage-gated Ca2+ channel; CaCC, Ca2+-activated Cl− channel.

  13. Ion channels in the regulation of uterinal smooth muscle tone Brainard  AM, Semin Cell Dev Biol. 2007;18(3):332-9. Big conductance Ca2+ activated K+ channel (BKCa), small conductance Ca2+ activated K+ channel (SK3), ATP-sensitive K+ channel (KATP) as a subtype of inward rectifier K+ channels (Kir), voltage dependent K+ channel (Kv)

  14. Strech-activated TREK-1, a type of two pore domain K+ channels (K2P) also regulates myometrial tone Buxton IL. et al, Acta Pharmacol Sin. 2011;32(6):758-64

  15. Pregnancy, hypoxia and K+ ion channels Zhu R et al. Curr Vasc Pharmacol. 2013;11(5):737-47. - + - + - -

  16. Subfamily members of voltage dependent K+ channels (Kv.7 and Kv.11) in the regulation of uterinal tone Greenwood IA, Tribe RM.Exp Physiol. 2014;99(3):503-9

  17. Transient receptor potential channels (TRPC) in smooth muscle cells – link to intracellular signaling Gonzalez-Cobos JC1, Trebak M,Front Biosci (Landmark Ed). 2010 Jun 1;15:1023-3 Phospholipase C (PLC), phosphatidylinositol 4,5-bisphosphate (PIP2), inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG), stromal interactive molecule (STIM1), store-operated channel (Orai1), transient receptor potential channel (TRPC), transcription factors: nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), cAMP response element-binding protein (CREB)

  18. Surface coupling between junctional sarcoplasmic reticulum (SR) and plasma membrane: leaflets of SR and cell membranes are separated by an 12- to 20-nm gap. Jaggar JH et al. Am J Physiol Cell Physiol 2000;278:C235-C256

  19. A crosstalk between the plasma membrane and sarcoplasmic reticulum involving Ca2+ and K+ channels in smooth muscle cells Jaggar JH. et al. Am J Physiol Cell Physiol 2000;278:C235-C256

  20. Possible mechanisms of action of PKA/PKG and PKC on Ca2+sparks, BKCa channels, and SR Ca2+-ATPase in arterial smooth muscle cells. Jaggar JH. et al. Am J Physiol Cell Physiol 2000;278:C235-C256

  21. Endothelial nitric oxide influence the tone through modulation of ion channels in smooth muscle cell of human umbilical artery Martin P. et al., Reprod Sci. 2014 April; 21(4): 432–441. NO: nitric oxide; KV: voltage-dependent K+ channels (different subfamilies); BKCa: big conductance, voltage- and Ca2+-sensitive K+ channel; SKCa: small conductance Ca2+-sensitive K+ channels; K2P: 2-pore domains K+ channels; KIR, inward rectifier K+ channels. Intermediate conductance Ca2+-sensitive K+ channels (IKCa), and ATP-sensitive K+ channels (KATP) are not included because the evidence about their presence in HUA is either weak (KATP) or altogether not present in the literature (IKCa). 1/ basal tone, 2/ agonist-induced contraction 3/ regulation by endothelium

  22. Some basic properties of ionic regulation of smooth muscle tone • Smooth muscle function is mainly regulated by the voltage operated (or dependent, or gated) Ca2+ channels (VOCC or VDCC or VDC or VGCC) • Typically, a large majority of other ion channels modulate membrane potential that regulates VOCC • Most types of smooth muscle cells are „electrically silent”- in contrast to nerves or skeletal muscles-; no action potential is generated (resting membrane potential is about -50 mV) • Ion channels maintain resting (basal) tension, modulate agonist- induced contractions and vasodilations by endothelial/ interstitial cell-derived factors

  23. Current research • Research focuses mainly on K+ channels in the regulation of smooth muscle tone of different organs (vascular, bronchial, uterinal) – an exception may be the gastrointestinal tract • A typical ion channel is still considered to be a receptor without cellular effector, however, some ion channels reveal a complex interaction with intracellular signaling mechanisms. • This ‘crosstalk’ may lead not only to immediate changes in their tone, but in addition to modifying the cellular phenotype of the smooth muscle cells (see TRPC channels)

More Related