Modulation of the Ca2+-Activated Large Conductance K+ Channel by Intracellular pH in Human Renal Proximal Tubule Cells.

Abstract

sensitive large conductance (big) K ϩ channels (BK channels) have been reported in the cell membranes of a variety of tissues [1,2]. An elevation of cytoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] i ) and depolarization of the membrane commonly stimulates activity of the BK channels [1][2][3]. It has already been proved by the use of cloned BK channels that the channel protein possesses the Ca 2ϩ -binding sites [4,5] and the voltagesensing domain [6,7]. Besides Ca 2ϩ and voltage, other factors such as ATP [8-11], pH [8, 9, 12-21], and Mg 2ϩ [19,[22][23][24] were also reported to modulate BK channels. Among these factors, intracellular pH (pH i ) is one of the significant factors that affect channel activity [8,9,[12][13][14][15][16][17][18][19][20][21], i.e., channel activity is inhibited by intracellular acidification and stimulated by its alkalization. Although the mechanism for pH i effects on channel activity was not precisely understood, two different mechanisms have been proposed. One is that an increased cytoplasmic H ϩ can compete with Ca 2ϩ in binding to the same sites, thereby inhibiting channel activity [14][15][16], whereas the other is that the pH i -mediated change in channel activity is not competitive with Ca 2ϩ [17]. Moreover, it was demonstrated that the conductance of some BK channels was reduced by lowering pH i and enhanced by raising it [9,15,20].In the renal tubules, BK channels have been reported in cultured rabbit proximal tubule cells [25]

Molecular Diversity and Regulation of Renal Potassium Channels

“…Several Kv channels have been detected in the apical membrane of the proximal tubule by patch clamp and immunocytochemistry (see Table 1). For example, Ca 2ϩ -activated, maxi-K ϩ type have been observed in cultured proximal tubule cells (42,204,205,262,380,548) and in proximal tubule bush-border membranes (666). In addition, calcium-insensitive, voltage-gated K ϩ channels have also been detected.…”

“…Ca 2ϩ -activated large-conductance (200 -300 pS; see Figs. 3, 4B, and 5; Table 2) or maxi-K ϩ channels have been identified in the apical membrane of cultured proximal tubule cells (42,204,205,262,380,548) and in the brush border of rabbit proximal tubules (666). These channels are activated by mechanical stretch and membrane depolarization.…”

BK channels in the kidney: role in K+secretion and localization of molecular components

“…Some (29,37), but not all (60), groups have reported BK channels in the proximal tubule. Interestingly, BK channels in the kidney tubule are activated by membrane stretch (101).…”