Effects of diadenosine polyphosphates, ATP and angiotensin II on membrane voltage and membrane conductances of rat mesangial cells

TY - JOUR

T1 - Effects of diadenosine polyphosphates, ATP and angiotensin II on membrane voltage and membrane conductances of rat mesangial cells

AU - Kleta, R

AU - Hirsch, J

AU - Heidenreich, Stefan

AU - Schlüter, H

AU - Zidek, W

AU - Schlatter, E

PY - 1995/9

Y1 - 1995/9

N2 - Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure Vm and gm. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5´-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the Vm values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agonist-induced changes of Vm, all data were pooled. The Vm of all the cells was -44 +/- 1 mV (n = 169) and gm was 15.9 +/- 1.8 nS (n = 141). Ion-exchange experiments showed the presence of a K+ and a non-selective cation conductance in resting MC whereas a Cl- conductance or a Na+-selective conductance could not be observed. Ap3A, Ap4A, Ap5A, AP6A and ATP each at a concentration of 5 micromol/l, led to a significant depolarization of Vm by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 25), 3 +/- 1 mV (n = 23), 2 +/- 1 mV (n = 16), and 14 +/- 2 mV (n = 23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC50) as 6 micromol/l (n = 5-25), for ATP as 2 micromol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap4A 100 micromol/l increased gm significantly by 55 +/- 20% (n = 16), 100 micromol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize Vm (Ang II > ATP > Ap4A > Ap3A > Ap5A > Ap6A) by activation of a Cl- conductance and a non-selective cation conductance, as do ATP or Ang II.

AB - Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure Vm and gm. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5´-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the Vm values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agonist-induced changes of Vm, all data were pooled. The Vm of all the cells was -44 +/- 1 mV (n = 169) and gm was 15.9 +/- 1.8 nS (n = 141). Ion-exchange experiments showed the presence of a K+ and a non-selective cation conductance in resting MC whereas a Cl- conductance or a Na+-selective conductance could not be observed. Ap3A, Ap4A, Ap5A, AP6A and ATP each at a concentration of 5 micromol/l, led to a significant depolarization of Vm by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 25), 3 +/- 1 mV (n = 23), 2 +/- 1 mV (n = 16), and 14 +/- 2 mV (n = 23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC50) as 6 micromol/l (n = 5-25), for ATP as 2 micromol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap4A 100 micromol/l increased gm significantly by 55 +/- 20% (n = 16), 100 micromol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize Vm (Ang II > ATP > Ap4A > Ap3A > Ap5A > Ap6A) by activation of a Cl- conductance and a non-selective cation conductance, as do ATP or Ang II.

KW - Adenosine

KW - Adenosine Triphosphate

KW - Angiotensin II

KW - Animals

KW - Cell Line

KW - Dinucleoside Phosphates

KW - Glomerular Mesangium

KW - Hypertension

KW - Kinetics

KW - Membrane Potentials

KW - Patch-Clamp Techniques

KW - Potassium Channels

KW - Rats

KW - Rats, Inbred SHR

KW - Rats, Inbred WKY

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - SCORING: Journal article

C2 - 7478923

VL - 430

SP - 713

EP - 720

JO - PFLUG ARCH EUR J PHY

JF - PFLUG ARCH EUR J PHY

SN - 0031-6768

IS - 5

ER -