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Published on: January 7, 2019
Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances
Re Dixon1, Sj Hwang, Fc Britton
1Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
Background And Purpose:
Spontaneous electrical activity, termed slow waves, drives rhythmic, propulsive contractions in the smooth muscle of the oviduct (myosalpinx). Myosalpinx contractions cause egg transport through the oviduct. Agents that disrupt slow wave pacemaker activity will therefore disrupt myosalpinx contractions and egg transport. Caffeine is commonly used as a ryanodine receptor agonist and has been previously associated with delayed conception. Here we assessed the effects of caffeine on pacemaker activity in the murine myosalpinx.
Experimental Approach:
The effects of caffeine on electrical pacemaker activity were studied using intracellular microelectrode and isometric force measurements on intact oviduct muscle preparations. Responses to caffeine were compared with responses caused by 3-isobutyl-1-methylxanthine (IBMX) and forskolin.
Key Results:
Caffeine caused hyperpolarization of membrane potential and inhibited slow wave generation and myosalpinx contractions. The effects of caffeine could be mimicked by the K(ATP) channel agonist pinacidil and antagonized by the K(ATP) channel antagonist glibenclamide. Caffeine is known to inhibit cyclic nucleotide phosphodiesterases (PDEs), leading to an increase in cytosolic cAMP and stimulation of downstream cAMP-dependent mechanisms. The effects of caffeine were mimicked by the PDE inhibitor, IBMX, and the adenylyl cyclase activator forskolin. These effects were also reversed by glibenclamide.
Conclusions And Implications:
These results suggest that caffeine activates K(ATP) channels in oviduct myosalpinx. Since caffeine abolishes slow waves and associated contractions of the myosalpinx, it would have a negative effect on egg transport through the oviduct and may contribute to the documented delayed conception in women consuming caffeinated beverages.
Insights
Caffeine inhibits oviduct muscle contractions by activating K(ATP) channels, potentially delaying egg transport and conception. This study investigates caffeine
Area of Science:
- Reproductive biology
- Smooth muscle physiology
- Pharmacology
Background:
- Oviduct (myosalpinx) smooth muscle contractions, driven by slow waves, are crucial for egg transport.
- Caffeine, a ryanodine receptor agonist, is linked to delayed conception.
Purpose of the Study:
- To investigate the effects of caffeine on pacemaker activity in the murine myosalpinx.
- To determine the cellular mechanisms underlying caffeine's action on oviduct smooth muscle.
Main Methods:
- Intracellular microelectrode recordings and isometric force measurements were used on oviduct muscle preparations.
- Responses to caffeine were compared with those of IBMX (a PDE inhibitor) and forskolin (an adenylyl cyclase activator).
- The roles of K(ATP) channels were assessed using agonists (pinacidil) and antagonists (glibenclamide).
Main Results:
- Caffeine caused hyperpolarization of the membrane potential, inhibiting slow wave generation and myosalpinx contractions.
- Caffeine's effects were mimicked by K(ATP) channel activation and PDE inhibition (IBMX, forskolin).
- Glibenclamide antagonized caffeine's effects, indicating K(ATP) channel involvement.
Conclusions:
- Caffeine activates K(ATP) channels in the oviduct myosalpinx.
- By abolishing slow waves and contractions, caffeine negatively impacts egg transport.
- Caffeine's action on oviduct function may explain its association with delayed conception.
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