Caffeine‐induced decreases in the inward rectifier potassium and the inward calcium currents in rat ventricular myocytes

Abstract

The effects of high (20 mm) concentrations of caffeine were studied on the transmembrane voltage and currents in rat single ventricular myocytes by the whole cell configuration of the patch clamp technique. Rapid application of caffeine released Ca2+ from the sarcoplasmic reticulum and induced a Ni2+‐sensitive transient inward current with concomitant change of the transmembrane voltage from −72.6 ± 0.4 to −68.0 ± 0.6 mV (n = 4). Maintained application of caffeine lengthened the action potential duration (APD90) from 66.7 ± 16.9 to 135.1 ± 34.1 ms (n = 4) and depressed the amplitude of both the inward rectifier potassium and the inward calcium currents. It is concluded that these effects of caffeine should be recognized when it is used as a tool to study electromechnical coupling.

NAADP Controls Cross-talk between Distinct Ca2+ Stores in the Heart

“…The SR Ca 2ϩ content was evaluated by rapid application of 10 mM caffeine to release the stored Ca 2ϩ , and the resultant Ca 2ϩ transient was measured (29). When assessed 45 s after photolysis of 5 M caged-NAADP, the Ca 2ϩ signal caused by rapid application of 10 mM caffeine was significantly increased by 21 Ϯ 4% (Fig.…”

Inhibition of human TREK-1 channels by caffeine and theophylline

“…Caffeine has been reported to inhibit potassium channels in a number of cell types, including mammalian ventricular myocytes (Sanchez-Chapula, 1992;Varro et al, 1993;Cui and Terrar, 1995;Chorvatova and Hussain, 2003), smooth muscle cells (Noack et al, 1990;Teramoto et al, 2000), dissociated chick autonomic ganglion neurons and pineal cells (Reiser et al, 1996), taste receptor cells (Zhao et al, 2002) and rat anterior pituitary cells (Kramer et al, 1994). Theophylline, too, has been shown to modulate potassium channels (Yamamoto et al, 1995;Schroder et al, 2000).…”

Effects of caffeine and 3‐isobutyl‐1‐methylxanthine on voltage‐activated potassium currents in vertebrate neurones and secretory cells

“…A structurally related methylxanthine, IBMX, also caused inhibition of voltage-activated K+ currents in chick ciliary ganglion neurones at millimolar concentrations. Previous studies have shown that millimolar concentrations of caffeine inhibit voltage-dependent K+ currents in rat ventricular myocytes (Sanchez-Chapula, 1992;Varro et al, 1993) and guinea-pig portal vein (Noack et al, 1990), although these effects were not described in detail. IBMX has been shown to inhibit a voltage-activated tetraethylammonium-sensitive K+ current in rat sensory neurones (Usachev et al, 1995).…”

“…The biophysical properties of the caffeine-sensitive K+ channels are clearly different in some of these cell types. For example, one of the caffeine-sensitive currents in ventricular myocytes is a Ba2+ -sensitive inward rectifier (Varro et al, 1993). This suggests a direct effect on conserved pore regions of the channel molecules as it is unlikely that the same regulatory cascades could result in blockade of K+ channels in all of these preparations (see below).…”

“…In this regard, there are data showing that millimolar concentrations of caffeine can inhibit voltage-dependent K+ currents in mammalian ventricular myocytes (Sanchez-Chapula, 1992;Varro et al, 1993) and vascular smooth muscle (Noack et al, 1990) as well as voltage-activated Na' channels in ventricular myocytes (Habuchi et al, 1991). To date, there have been no studies describing direct effects of caffeine on voltage-activated K+ channels in neurones or secretory cells, even though this compound is widely used in studies of those cell types (reviewed by Pozzan et al, 1994).…”