EFFECT OF CISPLATIN ON THE TRANS-EPITHELIAL POTENTIAL DIFFERENCE OF RAT DISTAL TUBULE

Cisplatin, an effective anti-tumor agent, has significant effects on renal function including reduced glomerular filtration rate and K and Mg wasting. Cisplatin increases Na conductance across the isolated frog skin, an effect which was inhibited by amiloride. The influence of cisplatin on the transepithelial potential difference (PD) of distal nephron segments of the rat kidney was investigated. Measurements were made under free-flow conditions and during distal microperfusion. When cisplatin was infused i.v. in a dose of 2 mg/kg h, the mean free-flow PD in late distal segments (cortical collecting tubules) increased from -18.5 .+-. 1.4 mV (N = 37) to -31.2 .+-. 1.4 mV (N = 36) (P < 0.001). The large negative PD seen with cisplatin was abolished with i.v. amiloride, a mean PD of + 0.9 .+-. 1.5 mV (N = 22) (P < 0.001) being obtained, similar to a PD of + 1.9 .+-. 1.5 mV (N = 39) found in control animals infused with amiloride. Perfusion of individual late distal segments with artificial plasma ultrafiltrate yielded a mean control PD of -12.4 .+-. 1.2 mV (N = 21) and a significantly higher PD of -17.5 .+-. 1.5 mV (N = 24) (P < 0.01) when cisplatin (10-3 M) was added to the perfusate. The addition of amiloride to these perfusates reduced the mean PD to -3.2 .+-. 0.5 mV (N = 19) and -3.6 .+-. 0.7 mV (N = 17), respectively. Cisplatin had no effect on the PD of early distal segments under either free-flow or microperfusion conditions. Cisplatin increases the magnitude of the negative PD in late distal segments of the rat kidney but does not influence the early distal PD. Amiloride prevents the cisplatin-induced PD change in the late distal tubule.