Number 24, 2004
Angina Pectoris

Glossary

Gary D. Lopaschuk

ATP-sensitive K⁺- channels
ATP-sensitive potassium (KATP) channels are potassium channels that are present in either the plasma membrane of the cell, or the mitochondrial membrane of the cell. These channels are inhibited by ATP, and the KATP in the plasma membrane serve to couple the metabolic status of the cell to its membrane potential. KATP regulates a number of cell actions, including muscle contractility (skeletal, cardiac and vascular smooth muscle). The opening of sarcolemmal and mitochondrial ATP-sensitive K(+) (KATP) channels in the heart is believed to mediate ischemic preconditioning, a phenomenon whereby brief periods of ischemia/reperfusion protect the heart against myocardial infarction.

Bamiphylline
Bamiphylline is a specific A1 adenosine receptor antagonist. By inhibiting A1 receptors it antagonizes the actions of adenosine on these receptors. This includes any cardioprotective effects of adenosine in the ischemic heart.

cGMP
cGMP stands for cyclic guanosine monophosphate. It is a very important intracellular signalling molecule in cells. In smooth muscle, an increase in cGMP results in vasodilation. The vasodilator effects of nitric oxide (NO) are mediated by cGMP.

Guanylate cyclase
Guanylate cyclase is an enzyme that catalyzes the formation of cGMP from guanosine triphosphate. Guanylate cyclase is a target of nitric oxide (NO), and is primarily responsible for NO mediated vasodilation.

I_f current
I_f is the abbreviation for a current that actively hyperpolarizes cells. The “f” stands for “funny” because this unusual current hyperpolarizes cells. I_f current is primarily present in the autonomic tissue of the heart (i.e sinoatrial and AV node). It contributes to the phase 4 depolarization of the cell.

Membrane phospholipid turnover
Cellular membranes consist of a number of phospholipids that are arranged in a bilayer. There are a number of different phospholipids in these membranes. These phospholipids are not static and are constantly turning over. Some phospholipids, such as phosphatidyl inositol, can turnover quite rapidly, resulting in the production of products that are important in cellular signalling processes (i.e. inositol triphosphate and diacylglycerol).

Mitochondrial K⁺-ATP channels
Mitochondrial ATP-sensitive potassium (KATP) channels are potassium channels that are present in the mitochondrial membrane of cells. These channels are inhibited by ATP. The opening of the mitochondrial ATP-sensitive K(+) (KATP) channels in the heart is believed to have cardioprotective effects in the setting of ischemia and ischemia and reperfusion. Despite a major research effort, the molecular characterization of the mitochondrial K⁺-ATP channel remains unknown.

Na⁺/H⁺ exchanger
The Na⁺/H⁺ exchanger is a membrane ion transporter that exchanges Na⁺ for H⁺. In the heart, it is one of a number of pathways to extrude protons (H⁺) from the heart. However, this is coupled with a net inward flux of Na+. During and following ischemia, Na⁺/H⁺ exchanger activity increases, due to the ischemic-induced increase in intracellular acidosis. The increased Na⁺/H⁺ exchanger activity can lead to Na⁺ overload in the ischemic heart, which can decrease cardiac efficiency (energy is needed to extrude this Na⁺) and contribute to cell injury.

Phosphodiesterase type 5 (PDE5)
Phosphodiesterases are enzymes that cleave cyclic nucleotides such as cAMP and cGMP. PDE 5 is a phosphodiesterase isoform that cleaves cGMP. Inhibition of PDE5 results in smooth muscle relaxation, and is the target for sildenafil (Viagra). This explains the coronary vasodilatory effect of sildenafil, as well as the effects on penial erection.

Tumor necrosis factor (TNF-α)
Tumor necrosis factor (TNF-α) is a cytokine that acts via receptors to mediate a number of biological effects, including the inflammatory response. The role of cytokines in the pathogenesis of systolic heart failure (HF) has been well established. TNF-α can also activate the intrinsic mitochondrial death pathway that is responsible for the cardiac myocyte apoptosis.

Subtypes (A₁ and A₂) of surface membrane P1 receptors
Purinergic receptors (designated “P” receptors) use purine nucleotides as ligands. The P1 class of purinergic receptors use adenosine as a ligand. These P1 receptors can further be classified as A1, A2, and A3 receptors. The vasodilatory effects of adenosine are primarily mediated by binding to A2 receptors. The direct chronotropic effects of adenosine on the heart, and many of its cardioprotective actions are mediated by adenosine binding to A1 receptors. Ischemic preconditioning involves a series of intracellular events that are initiated with the activation of the A1 receptor, and end at the sensitive K+ ATP channels of the mitochondria. New evidence points to a role for adenosine in promoting neovascularization through a mechanism that requires interaction between the adenosine receptor subtype 2A (A(2A)R).