Effect of caffeine on K + efflux in frog skeletal muscle

Abstract

The exposure of frog skeletal muscle to caffeine (3-4 mM) generates an increase of the K+ (42K+) efflux rate coefficient (kK,o) which exhibits the following characteristics. First it is promoted by the rise in cytosolic Ca2+ ([Ca2+]i), because the effect is mimicked by ionomycin (1.25 microM), a Ca2+ ionophore. Second, the inhibition of caffeine-induced Ca2+ release from the sarcoplasmic reticulum (SR) by 40 microM tetracaine significantly reduced the increase in kK,o (DeltakK,o). Third, charybdotoxin (23 nM), a blocker of the large-conductance Ca2+-dependent K+ channels (BKCa channels) reduced DeltakK,o by 22%. Fourth, apamin (10 nM), a blocker of the small-conductance Ca2+-dependent K+ channels (SKCa channels), did not affect DeltakK,o. Fifth, tolbutamide (800 microM), an inhibitor of KATP channels, reduced DeltakK,o by about 23%. Sixth, Ba2+, a blocker of most K+ channels, did not preclude the caffeine-induced DeltakK,o. Seventh, omitting Na+ from the external medium reduced DeltakK,o by about 40%. Eight, amiloride (5 mM) decreased DeltakK,o by 65%. It is concluded that the caffeine-induced rise of [Ca2+]i increases K+ efflux, through the activation of: (1) two channels (BKCa and KATP) and (2) an external Na+-dependent amiloride-sensitive process.

Dual regulation of the ATP-sensitive potassium channel by caffeine

“…Among these channels, direct block of hERG channels (17), K ATP channels (36), delayed rectifier channels (59), (I A -like) transient outward potassium channels (54,59), some inwardly rectifying (9) and outward potassium currents (15,19,85), and L-type calcium channels (41) by caffeine has been suggested. In contrast, several studies have suggested that caffeine activates the intermediate-conductance K Ca (IK) channel currents (but not large-or small-conductance K Ca channels) in transfected HEK293 cells (68) and K Ca channels in guinea pig adrenal chromaffin cells (55) and increases potassium efflux in frog skeletal muscle (86). Here we report that caffeine exerts both activation (that is SURdependent and requires cGMP-PKG and Ca 2ϩ signaling; Figs.…”

“…It has also been demonstrated that caffeine at high concentrations acts as an inhibitor of several potassium channels, including depolarization-activated potassium channels in sympathetic neurons, secretory cells (59), taste receptor cells (93), and ventricular myocytes (67); calciumactivated potassium (K Ca ) channels in GH 3 pituitary cells (41), sympathetic neurons (59), secretory cells (59), vascular smooth muscle cells (54), and taste receptor cells (93); human ether a-go-go-related gene potassium (hERG) channels in transfected mammalian cells (17); Kir channels in GH 3 rat anterior pituitary cells (9), ventricular myocytes (15,67,85), and taste receptor cells (93); K ATP channels in pancreatic ␤-cells (36) and smooth muscle cells (80); and recombinant two-pore domain potassium channel TREK-1 in Chinese hamster ovary (CHO) cells (26). On the other hand, caffeine has also been shown to increase potassium efflux in skeletal muscle (86) and to activate K Ca channels in adrenal chromaffin cells (55). How caffeine modulates the K ATP channels in intact cells, however, was unclear, as the patch configuration (i.e., inside-out mode) used in previous studies (36,80) may not allow detection of channel modulation involving intracellular signaling; in addition, the ion channel conductance inhibited by caffeine in urethra (80) seems too small for nonvascular smooth muscle K ATP channels (37,89).…”

Caffeine‐induced depolarization in amphibian skeletal muscle fibres: role of Na+/Ca2+ exchange and K+ release

“…Recently we showed that in intact frog muscle, caffeine besides the activation of the NCX, promotes a marked increase in K + efflux which is also mediated by the increase in [Ca] i . A question to be asked then, is whether such a rise in K + efflux could increase the K + concentration ([K + ] o ) in restricted spaces like the T tubules, thus producing, in part, the observed depolarization (Figs 1 and 2) whose time course is similar to that of the rise of K + efflux (Venosa & Hoya 1999). On the other hand, under voltage clamp conditions, an increase in [K + ] o should displace i h in the same direction as that promoted by the forward mode activity of the NCX.…”

“…In frog skeletal muscle the rise of cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ) triggered by the exposure to 4 m M caffeine produces an increase in Ca 2+ efflux through a mechanism which, operationally, has all the characteristics of the Na + –Ca 2+ exchanger (NCX) (Hoya & Venosa 1995). In addition, the caffeine‐ induced rise in [Ca 2+ ] i produces a marked increase in K + efflux rate coefficient (Venosa & Hoya 1999). These two effects of caffeine are accompanied by a depolarization of the fibres.…”

Effects of halothane on the membrane potential in skeletal muscle of the frog

“…CTX‐sensitive BK Ca channels have been reported in many tissues including skeletal muscle ( Marty, 1989 ). In addition, in frog skeletal muscle, the release of Ca 2+ from the SR induced by caffeine promotes a rise in cytosolic Ca 2+ and an increase in K + efflux rate coefficients which was reduced by CTX, a blocker of BK Ca channels; insensitive to apamin, a blocker of small conductance Ca 2+ ‐dependent K + channels; reduced by tolbutamide, an inhibitor of K ATP channels; and insensitive to barium, a blocker of most K + channels ( Venosa & Hoya, 1999 ). Present observations suggest that halothane mimicked the effect of caffeine on skeletal muscle and led to a rise in [Ca 2+ ] i and to the activation of BK Ca channels.…”