Potassium channel blockers inhibit anion secretion in cultured rat epididymal epithelium.

Abstract

The effect of putative K channel blockers on anion secretion has been studied in primary monolayer cultures of rat epididymal cells using the short circuit current technique. Under basal conditions, monolayers had a transepithelial potential difference of about 2-3 mV, apical side negative and a short circuit current (SCC) of about 2 pA • cm-2. The transepithelial resistance was about 500 Q • cm2. Addition of adrenaline (0.23 pM, basolaterally) caused the SCC to rise to a peak value of about 10.5pA • cm-2 and then stabilized at about 4pA • cm-2 after 15 min. This rise in the short circuit current has previously been shown to be due to an increase in net anion secretion from the basolateral to the apical medium. In tissues stimulated with adrenaline, addition of barium (Ba) to the apical side did not affect the adrenaline-induced SCC, but addition to the basolateral side caused a dose-dependent inhibition of the current with an IC50 value (concentration required to inhibit 5000 of the current) of 0.92 mM. At Ba concentration of 5 mM, the adrenaline-induced SCC was completely abolished. There was no effect on transepithelial resistance. Addition of tetraethylamonium (TEA) (16 mM) to the apical or basolateral side had no significant effect on the adrenaline-stimulated SCC. Lidocaine and quinidine inhibited the adrenaline-stimulated SCC when added either to the apical or basolateral bathing solution. The IC50 values for lidocaine were 0.42 mM and 0.35 mM for basolateral and apical application, respectively. The IC50 values for quinidine were 0.062 mM and 0.050 mM for basolateral and apical application, respectively. In all cases there was no change in tissue resistance. It is proposed that in the basolateral membrane of the epididymal cells, there is a component which is sensitive to putative K channel blockers. It is likely that it is a K channel. As in other secretory cells, this channel plays an important role in secretion.

Electrophysiological studies of anion secretion in cultured human epididymal cells.

“…These carriers utilize the Na+ gradient energy generated by a Na+,K+-ATPase in the basolateral membrane to accumulate Cland HCO3inside the cells to above electrochemical equilibrium. The potassium ions which have entered the cells via the symport and the Na+,K+-ATPase leave the cell through a regulated K+ conductance pathway in the basolateral membrane (Wong, 1989). The Na+,K+-ATPase, the symport and the K+ channels act as one functional unit which serves to accumulate Cl-inside the cell to above electrochemical equilibrium (Petersen & Maruyama, 1984).…”