TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells

Silke Jung1, Rainer Strotmann, Günter Schultz

  • 1Institut für Pharmakologie, Freie Universität Berlin, 14195 Berlin, Germany.

Insights

This study identifies Transient Receptor Potential Canonical 6 (TRPC6) channels as key players in [Arg(8)]-vasopressin-induced calcium entry in aortic smooth muscle cells, crucial for vasoconstriction.

Area of Science:

  • Physiology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Mammalian transient receptor potential (TRP) channels are implicated in cellular signaling.
  • Calcium (Ca2+) influx is vital for vascular smooth muscle cell function, including vasoconstriction.

Purpose of the Study:

  • To investigate the role of TRP channels in [Arg(8)]-vasopressin (AVP)-induced Ca2+ entry in A7r5 aortic smooth muscle cells.
  • To identify specific TRPC isoforms involved in receptor-stimulated cation currents.

Main Methods:

  • Whole-cell patch-clamp recordings to analyze ion channel activity.
  • Stimulation of cells with AVP, G protein activators, and growth factors.
  • Northern hybridization to detect TRPC mRNA expression.

Main Results:

  • AVP induced Ca2+ release and influx in A7r5 cells.
  • A nonselective cation current, activated by AVP and G proteins, was identified.
  • This current was stimulated by 1-oleoyl-2-acetyl-sn-glycerol independently of protein kinase C.
  • Flufenamate enhanced the cation currents, similar to TRPC6.
  • TRPC1 and TRPC6 mRNA were detected in A7r5 cells.

Conclusions:

  • TRPC6 is suggested to be a molecular component of the receptor-stimulated Ca2+-permeable cation channels in vascular smooth muscle cells.
  • These findings contribute to understanding the molecular mechanisms of vasoconstriction.

Related Concept Videos

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
G Protein-coupled Receptors01:27

G Protein-coupled Receptors

G-protein-coupled receptors are ligand-binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that traverses the cell membrane seven times, creating intracellular and extracellular loops. The extracellular loops create a ligand-specific pocket which binds to neurotransmitters or hormones. The intracellular loops hold onto the G-protein.The G-protein, or guanine nucleotide-binding protein, is a large heterotrimeric complex. Its three subunits...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...