EFFECTS OF DIADENOSINE POLYPHOSPHATES, ATP AND ANGIOTENSIN-II ON MEMBRANE VOLTAGE AND MEMBRANE CONDUCTANCES OF RAT MESANGIAL CELLS

Diadenosine polyphosphates have been shown to influence renal perfusio n pressure. As mesangial cells may contribute to these effects we inve stigated the effects of diadenosine triphosphate (Ap(3)A), diadenosine tetraphosphate (Ap(4)A), diadenosine pentaphosphate (Ap(5)A) and diad enosine hexaphosphate (Ap(6)A) on membrane voltage (V-m) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-te rm culture. We applied the patch-clamp technique in the fast-whole-cel l configuration to measure V-m and g(m). To compare the effects of dia denosine polyphosphates with hitherto known agonists we also tested ad enosine 5'-triphosphate (ATP) and angiotensin II (Ang II). As there wa s no significant difference in the V-m values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agon ist-induced changes of V-m, all data were pooled. The V-m of all the c ells was -44 +/- 1 mV (n = 169) and g(m) was 15.9 +/- 1.8 nS (n = 141) . Ion-exchange experiments showed the presence of a K+ and a non-selec tive cation conductance in resting MC whereas a Cl- conductance or a N a+-selective conductance could not be observed. Ap(3)A, Ap(4)A, Ap(5)A , AP(6)A and ATP each at a concentration of 5 mu mol/l, led to a signi ficant depolarization of V-m by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 2 5), 3 + 1 mV (n = 23), 2 + 1 mV (n = 16), and 14 +/- 2 mV (n = 23), re spectively. For Ap(4)A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC(50)) as 6 mu mol/l (n = 5-25), for ATP as 2 mu mol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap(4)A 100 mu mol/l increased g(m) significantly by 55 +/- 20% (n = 16), 100 mu mol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize V-m (Ang II > ATP > Ap(4)A > Ap(3)A > Ap(5)A > Ap(6)A) by activation of a Cl- c onductance and a non-selective cation conductance, as do ATP or Ang II .