The inhibitory action of caffeine on calcium currents in isolated intestinal smooth muscle cells

Abstract

The patch-clamp method has been used to investigate the action of caffeine on the calcium current (ICa) in single isolated smooth muscle cells of the guinea-pig ileum. Caffeine (10 mM) substantially inhibited ICa. This effect occurred in a biphasic manner and it was not due either to activation of additional ionic currents of opposite direction nor to inhibition of phosphodiesterase activity. It strongly depended upon the ethylenebis-(oxonitrilo)tetraacetate (EGTA) concentration in the pipette solution. When there was K+ in the pipette solution, application of caffeine evoked a transient Ca-dependent K+ current and an abrupt and transient increase in the frequency of channel openings. Such well-known blockers of Ca release as procaine and ruthenium red strongly decreased ICa. Ryanodine had only little effect on ICa, but application of caffeine in the presence of ryanodine led to a complete and irreversible inhibition of ICa. The results of experiments involving different EGTA concentrations and comparison of the time courses of all caffeine-induced phenomena clearly indicated that only the initial, transient component of the ICa inhibition by caffeine was related to a Ca-dependent inactivation of Ca channels, evoked as a result of Ca release from intracellular stores. The tonic component of ICa inhibition was probably due to a direct blocking action of caffeine on Ca channels.

Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle

“…The effect on the Ba 2ϩ current is not due to caffeine-induced cAMP phosphodiesterase (PDE) inhibition (Poch and Umfahrer, 1976), as nonmethylxanthine cAMP PDE inhibitors do not inhibit the Ba 2ϩ current. These findings are consistent with data obtained in freshly isolated smooth muscle cells from the guinea pig ileum (Zholos et al, 1991), where caffeine (10 mM) substantially inhibits depolarization pulse-induced Ca 2ϩ currents. This latter effect occurs in a biphasic manner: a transient component, associated with Ca 2ϩ -dependent inactivation of Ca 2ϩ L resulting from SR Ca 2ϩ release, and a tonic component.…”

“…Caffeine also transiently inhibits Ca 2ϩ L -mediated currents in freshly isolated smooth muscle cells from the guinea pig ileum (Zholos et al, 1991), an effect that is inhibited by the RyR blockers procaine and ruthenium red, suggesting that this transient inhibition of Ca Second, a long exposure time to caffeine (more than several minutes) prevents access of Ca 2ϩ influx to the myofilaments in the porcine carotid artery (Rembold et al, 1995). In this tissue, caffeine (20 mM) first induces synchronized transient increases in aequorin-reported [Ca 2ϩ ] cyt , fura-2-reported [Ca 2ϩ ] cyt , LC 20 phosphorylation, and force peaking within 1.5 min.…”

Caffeine‐evoked, calcium‐sensitive membrane currents in rabbit aortic endothelial cells

“…Caffeine has also been shown to inhibit voltagedependent calcium channels in smooth muscle cells (Hughes et al, 1990;Zholos et al, 1991). Additionally, we found that prolonged exposure of endothelial cells to caffeine induces cell shrinkage.…”

Inhibitory effects of histamine and bradykinin on calcium current in smooth muscle cells isolated from guinea‐pig ileum.

“…Figure 4B shows inhibition of 'ca by 10 mM caffeine when the pipette solution contained 30 mMi EGTA. Histamine and BK had been applied to this cell and neither had affected 'ca~Therefore, at least part of the sustained suppression seen with caffeine (refer also to Zholos, Baidan & Shuba, 1991) occurred by a mechanism distinct from that activated by histamine or BK.…”