Regulation of filtration rate by glomerular mesangial cells in health and diabetic renal disease

James D. Stockand, Steven C. Sansom

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The rate of renal filtration is in large part responsible for volume and electrolyte balance in an organism. Integral components of the renal glomerulus are the mesangial cells (MCs), excitable renal pericytes that regulate the glomerular filtration rate by modulating the surface area of the capillaries. Similar to vascular smooth muscle, the signal transduction pathways and ion selective channels regulating isotonic and isometric contraction of MCs are dependent on the voltage-gated Ca influx. During the response to contractile agonists, both CI and nonselective cation channels play critical roles to depolarize the membrane potential and activate Ca channels. The relaxation pathways involve a negative-feedback mechanism that counteracts mesangial contraction by regulating voltage-dependent Ca signaling. Part of the feedback response involves the activation of plasmalemmal K channels, which hyperpolarize the membrane potential and inhibit voltage-gated Ca entry. This calcium- and voltage-activated feedback K (BK(Ca)) channel shares biophysical, pharmacologic, and molecular properties with the BK(Ca) channels identified in brain and muscle, and with the sio gene product as expressed in Xenopus laevis oocytes. Systemic hormones, such as atrial natriuretic peptide, and paracrine factors, such as nitric oxide (NO), use guanosine 3',5'cyclic monophosphate (GMP) as a second messenger and enhance the gain in this feedback system by decreasing the voltage and Ca activation thresholds for BK(Ca). Diabetes mellitus is often associated with high rates of glomerular filtration, mesangial expansion, and secretory abnormalities of the basement membrane. NO-mediated increases in negative-feedback regulation of mesangial tone may attribute, in part, to the pathology of hyperfiltration. Stimulation of inducible nitric oxide synthetase in glomerular MCs by inflammatory cytokines is a possible positive-feedback pathway that contributes to further glomerular destruction. In addition, high ambient glucose, through modulation of BK(Ca) activity, facilitates MC relaxation and thus propagates hyperfiltration. Since cellular arachidonic acid is metabolically linked to extracellular glucose, this fatty acid is a possible mediator of the pathologic actions of hyperglycemia. Clarification of the signal transduction pathways and ionic mechanisms regulating the normal and dysfunctional tones of MCs is essential for rational clinical management of glomerular disease and critical to understanding fluid and electrolyte homeostasis.

Original languageEnglish (US)
Pages (from-to)971-981
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume29
Issue number6
DOIs
StatePublished - Jun 1997

Fingerprint

Mesangial Cells
Kidney
Health
Large-Conductance Calcium-Activated Potassium Channels
Glomerular Filtration Rate
Membrane Potentials
Signal Transduction
Nitric Oxide
Isotonic Contraction
Glucose
Pericytes
Isometric Contraction
Water-Electrolyte Balance
Cyclic GMP
Xenopus laevis
Atrial Natriuretic Factor
Second Messenger Systems
Disease Management
Ion Channels
Vascular Smooth Muscle

Keywords

  • Arachidonic acid
  • Atrial natriuretic peptide
  • Diabetes
  • Guanosine 3',5'-cyclic monophosphate-dependent kinase
  • Ion channels
  • Kidney disease
  • Nitric oxide

ASJC Scopus subject areas

  • Nephrology

Cite this

Regulation of filtration rate by glomerular mesangial cells in health and diabetic renal disease. / Stockand, James D.; Sansom, Steven C.

In: American Journal of Kidney Diseases, Vol. 29, No. 6, 06.1997, p. 971-981.

Research output: Contribution to journalArticle

@article{acc3711f497c47c796e4e0388599ba58,
title = "Regulation of filtration rate by glomerular mesangial cells in health and diabetic renal disease",
abstract = "The rate of renal filtration is in large part responsible for volume and electrolyte balance in an organism. Integral components of the renal glomerulus are the mesangial cells (MCs), excitable renal pericytes that regulate the glomerular filtration rate by modulating the surface area of the capillaries. Similar to vascular smooth muscle, the signal transduction pathways and ion selective channels regulating isotonic and isometric contraction of MCs are dependent on the voltage-gated Ca influx. During the response to contractile agonists, both CI and nonselective cation channels play critical roles to depolarize the membrane potential and activate Ca channels. The relaxation pathways involve a negative-feedback mechanism that counteracts mesangial contraction by regulating voltage-dependent Ca signaling. Part of the feedback response involves the activation of plasmalemmal K channels, which hyperpolarize the membrane potential and inhibit voltage-gated Ca entry. This calcium- and voltage-activated feedback K (BK(Ca)) channel shares biophysical, pharmacologic, and molecular properties with the BK(Ca) channels identified in brain and muscle, and with the sio gene product as expressed in Xenopus laevis oocytes. Systemic hormones, such as atrial natriuretic peptide, and paracrine factors, such as nitric oxide (NO), use guanosine 3',5'cyclic monophosphate (GMP) as a second messenger and enhance the gain in this feedback system by decreasing the voltage and Ca activation thresholds for BK(Ca). Diabetes mellitus is often associated with high rates of glomerular filtration, mesangial expansion, and secretory abnormalities of the basement membrane. NO-mediated increases in negative-feedback regulation of mesangial tone may attribute, in part, to the pathology of hyperfiltration. Stimulation of inducible nitric oxide synthetase in glomerular MCs by inflammatory cytokines is a possible positive-feedback pathway that contributes to further glomerular destruction. In addition, high ambient glucose, through modulation of BK(Ca) activity, facilitates MC relaxation and thus propagates hyperfiltration. Since cellular arachidonic acid is metabolically linked to extracellular glucose, this fatty acid is a possible mediator of the pathologic actions of hyperglycemia. Clarification of the signal transduction pathways and ionic mechanisms regulating the normal and dysfunctional tones of MCs is essential for rational clinical management of glomerular disease and critical to understanding fluid and electrolyte homeostasis.",
keywords = "Arachidonic acid, Atrial natriuretic peptide, Diabetes, Guanosine 3',5'-cyclic monophosphate-dependent kinase, Ion channels, Kidney disease, Nitric oxide",
author = "Stockand, {James D.} and Sansom, {Steven C.}",
year = "1997",
month = "6",
doi = "10.1016/S0272-6386(97)90476-5",
language = "English (US)",
volume = "29",
pages = "971--981",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Regulation of filtration rate by glomerular mesangial cells in health and diabetic renal disease

AU - Stockand, James D.

AU - Sansom, Steven C.

PY - 1997/6

Y1 - 1997/6

N2 - The rate of renal filtration is in large part responsible for volume and electrolyte balance in an organism. Integral components of the renal glomerulus are the mesangial cells (MCs), excitable renal pericytes that regulate the glomerular filtration rate by modulating the surface area of the capillaries. Similar to vascular smooth muscle, the signal transduction pathways and ion selective channels regulating isotonic and isometric contraction of MCs are dependent on the voltage-gated Ca influx. During the response to contractile agonists, both CI and nonselective cation channels play critical roles to depolarize the membrane potential and activate Ca channels. The relaxation pathways involve a negative-feedback mechanism that counteracts mesangial contraction by regulating voltage-dependent Ca signaling. Part of the feedback response involves the activation of plasmalemmal K channels, which hyperpolarize the membrane potential and inhibit voltage-gated Ca entry. This calcium- and voltage-activated feedback K (BK(Ca)) channel shares biophysical, pharmacologic, and molecular properties with the BK(Ca) channels identified in brain and muscle, and with the sio gene product as expressed in Xenopus laevis oocytes. Systemic hormones, such as atrial natriuretic peptide, and paracrine factors, such as nitric oxide (NO), use guanosine 3',5'cyclic monophosphate (GMP) as a second messenger and enhance the gain in this feedback system by decreasing the voltage and Ca activation thresholds for BK(Ca). Diabetes mellitus is often associated with high rates of glomerular filtration, mesangial expansion, and secretory abnormalities of the basement membrane. NO-mediated increases in negative-feedback regulation of mesangial tone may attribute, in part, to the pathology of hyperfiltration. Stimulation of inducible nitric oxide synthetase in glomerular MCs by inflammatory cytokines is a possible positive-feedback pathway that contributes to further glomerular destruction. In addition, high ambient glucose, through modulation of BK(Ca) activity, facilitates MC relaxation and thus propagates hyperfiltration. Since cellular arachidonic acid is metabolically linked to extracellular glucose, this fatty acid is a possible mediator of the pathologic actions of hyperglycemia. Clarification of the signal transduction pathways and ionic mechanisms regulating the normal and dysfunctional tones of MCs is essential for rational clinical management of glomerular disease and critical to understanding fluid and electrolyte homeostasis.

AB - The rate of renal filtration is in large part responsible for volume and electrolyte balance in an organism. Integral components of the renal glomerulus are the mesangial cells (MCs), excitable renal pericytes that regulate the glomerular filtration rate by modulating the surface area of the capillaries. Similar to vascular smooth muscle, the signal transduction pathways and ion selective channels regulating isotonic and isometric contraction of MCs are dependent on the voltage-gated Ca influx. During the response to contractile agonists, both CI and nonselective cation channels play critical roles to depolarize the membrane potential and activate Ca channels. The relaxation pathways involve a negative-feedback mechanism that counteracts mesangial contraction by regulating voltage-dependent Ca signaling. Part of the feedback response involves the activation of plasmalemmal K channels, which hyperpolarize the membrane potential and inhibit voltage-gated Ca entry. This calcium- and voltage-activated feedback K (BK(Ca)) channel shares biophysical, pharmacologic, and molecular properties with the BK(Ca) channels identified in brain and muscle, and with the sio gene product as expressed in Xenopus laevis oocytes. Systemic hormones, such as atrial natriuretic peptide, and paracrine factors, such as nitric oxide (NO), use guanosine 3',5'cyclic monophosphate (GMP) as a second messenger and enhance the gain in this feedback system by decreasing the voltage and Ca activation thresholds for BK(Ca). Diabetes mellitus is often associated with high rates of glomerular filtration, mesangial expansion, and secretory abnormalities of the basement membrane. NO-mediated increases in negative-feedback regulation of mesangial tone may attribute, in part, to the pathology of hyperfiltration. Stimulation of inducible nitric oxide synthetase in glomerular MCs by inflammatory cytokines is a possible positive-feedback pathway that contributes to further glomerular destruction. In addition, high ambient glucose, through modulation of BK(Ca) activity, facilitates MC relaxation and thus propagates hyperfiltration. Since cellular arachidonic acid is metabolically linked to extracellular glucose, this fatty acid is a possible mediator of the pathologic actions of hyperglycemia. Clarification of the signal transduction pathways and ionic mechanisms regulating the normal and dysfunctional tones of MCs is essential for rational clinical management of glomerular disease and critical to understanding fluid and electrolyte homeostasis.

KW - Arachidonic acid

KW - Atrial natriuretic peptide

KW - Diabetes

KW - Guanosine 3',5'-cyclic monophosphate-dependent kinase

KW - Ion channels

KW - Kidney disease

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=0030915470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030915470&partnerID=8YFLogxK

U2 - 10.1016/S0272-6386(97)90476-5

DO - 10.1016/S0272-6386(97)90476-5

M3 - Article

C2 - 9186087

AN - SCOPUS:0030915470

VL - 29

SP - 971

EP - 981

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 6

ER -