Coffee and Calcium: How caffeine works

“We like coffee here”

“And calcium channels”

They looked at each other and chuckled.  Then my PI looked at me and asked, “Do you know a good pharmacological way to open up calcium channels?...Caffeine!”

            While the molecular mechanisms of caffeine still require research, there is a decent understanding of how caffeine works.  Researchers know that caffeine in vertebrates does several things at the molecular level.  These include an increase in cAMP, an increase in the release of intracellular calcium, and the inhibition of acetylcholinesterase (1).  These three specific molecular mechanisms work to produce the caffeine jolt we associate with its consumption.

            Caffeine inhibits phosphodiesterases (PDE), which in turn increases cAMP which is normally regulated by PDEs.  As we know from class, cAMP is a second messenger, which aids in signal transduction in a number of biological pathways.  Among these pathways, cAMP helps to regulate the effects of adrenaline by helping the hormone cross the plasma membrane and reach its target receptor (2).  Therefore, when cAMP is increased in the cell, the effect of adrenaline is increased.  This helps to explain part of the sympathetic nervous system activation observed with caffeine consumption.

            Caffeine also increases the release of intracellular calcium.  This occurs when caffeine binds to ryanodine receptors.  While we have only really touched on about two types of calcium channels in class, it turns out there are actually far more than the scope of our class covers.  Ryanodine receptors happen to be one of these.  They are ligand-gated calcium channels which play regulatory roles in the release of intracellular calcium stores.  When caffeine binds to these receptors, their affinity for calcium increases, meaning the channel is activated at lower calcium concentrations, and can begin to release calcium from intracellular stores (1).  Calcium in turn can work to activate other pathways, including action potentials within the heart.

            The third molecular mechanism I thought was interesting is the effect of caffeine on acetylcholinesterase (1). Acetylcholinesterase works to degrade acetylcholine; however, if this enzyme is inhibited, acetylcholine will remain present and can continue to send messages to post-synaptic ganglia.

            The use of caffeine is still debated as beneficial or detrimental, though studies have linked coffee consumption to a decreased risk of type 2 diabetes, hypertension, obesity, depression, and Parkinson’s disease (3).  Personally, those are good enough reasons for me to keep activating my calcium channels and pour another cup of coffee!

1.Mustard JA. 2013 Oct. The buzz on caffeine in invertebrates: Effects on behavior and molecular mechanisms. Cellular and Molecular Life Sciences. DOI 10.1007/s00018-013-1497-8

2.Giraldo E, Hinchado M, and Ortega E. 2013 May. Combined activity of post-exercise concentrations of NA and eHsp72 on human neutrophil function: Role of cAMP. Journal of Cellular Physiology 228(9):1902-1906.

3. O’Keefe J, Bhatti S, Patil H, DiNicolatonio J, Lucan S, and Lavie C. 2013 Sep. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. Journal of the American College of Cardiology 62(12):1043-1051.