Electrophysiological analysis of effect of propranolol in rabbit S2 proximal straight tubule.
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 +/- 2.0 mV. Addition of 10(-4) mol/l of dl-propranolol to the basolateral solution rapidly depolarized Vb by 12.1 +/- 1.3 mV in 20 sec (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 delta Vb) occurred in a dose-dependent manner. In the presence of 1 mmol/l Ba++ in basolateral solution, propranolol-induced delta Vb was strongly inhibited. The stilbene derivative DIDS at 1 mmol/l did not change propranolol-induced delta Vb, whereas the elimination of Cl- from the ambient conditions increased propranolol-induced delta Vb. The minimization of the luminal Na(+)-coupled organic solute transporter by collapsing of the lumen did not inhibit propranolol-induced delta Vb, indicating the lack of effect of propranolol on luminal Na(+)-coupled transporters. Ouabain at 10(-3) mmol/l in the bath did not eliminate propranolol-induced delta Vb, 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.
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Y
Y
Kondo
Y
Y
Igarashi
K
K
Kudo
N
N
Takahashi
O
O
Ito
C N
CN
Inoue
I
I
Fujiwara
K
K
Abe
D000818:Animals; D001464:Barium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009248:Nadolol / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D009004:Monosaccharide Transport Proteins; D015221:Potassium Channels; D017923:Sodium-Hydrogen Exchangers; D001464:Barium; D009248:Nadolol; D011433:Propranolol; D011188:Potassium