KONDO, Y., IGARASHI, Y., KUDO, K., TAKAHASHI, N., ITO, O., INOUE, C.N., FUJIWARA, I. and ABE, K.
Electrophysiological Analysis of Effect of Propranolol in Rabbit S2 Proximal Straight Tubule. Tohoku J. Exp. Med., 1994,
172 (1), 29-38-The effect of dl-propranolol on the basolateral membrane potential (Vb) of in vitro microperfused S2 proximal straight tubules of the rabbit kidney was examined using conventional microelectrode techniques. In the steady-state condition, the average of 23 measurements of Vb was -44.8±2.0mV. Addition of 10
-4mol/l of dl-propranolol to the basolateral solution rapidly depolarized Vb by 12.1±1.3mV in 20sec (
n=15). The same dose of d-isomer of propranolol, which has no beta-blocking effect, also depolarized Vb to a similar extent. The non-selective beta-blocker nadolol, which possesses no membrane stabilising activity, had no effect on Vb. Depolarization of Vb by dl-propranolol in 20 seconds (propranolol-induced ΔVb) occurred in a dose-dependent manner. In the presence of 1mmol/l Ba
++ in basolateral solution, propranolol-induced ΔVb was strongly inhibited. The stilbene derivative DIDS at 1mmol/l did not change propranolol-induced ΔVb, whereas the elimination of Cl
- from the ambient conditions increased propranolol-induced ΔVb. The minimization of the luminal Na
+-coupled organic solute transporter by collapsing of the lumen did not inhibit propranolol-induced ΔVb, indicating the lack of effect of propranolol on luminal Na
+-coupled transporters. Ouabain at 10
-3mmol/l in the bath did not eliminate propranolol-induced ΔVb, indicating the presence of a target transporter other than Na
+/K
+ ATPase for propranolol. These results suggest the following; 1) propranolol has a depolarizing effect on Vb in proximal tubule; 2) the effect of propranolol is independent of Cl
- transport or Na
+-coupled transporters in the luminal membrane; 3) propranolol depolarizes Vb by inhibiting the K
+ channel in the basolateral membrane of S2 proximal tubule.
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