Ca2*-entry blockers

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

While the molecular identity of the capacitative Ca2+ entry channel is not known, a candidate is a homolog of the Drosophila mutant trp. This photoreceptor mutant is incapable of maintaining a sustained photoreceptor potential. This phenotype could be mimicked by the calcium entry blocker lanthanum, and it was suggested that the related defect is a failure of Ca2+ entry. 

Blaustein 2-aminoethoxydiphenyl borate (2-APB) is used as a selective blocker of InsP3 receptors. However, I think I have seen recent papers showing that 2-APB also blocks Ca2+ entry in some way. Do you think it blocks Ca2+ entry and reduces the tonic component in this way ... 

Intracellular Ca2+ waves have been observed both in the absence of Ca2+ in the bathing solution and in the presence of non-specific blockers of transmembrane Ca2+ entry, such as La3+. Thus, the primary source of Ca2+ for intracellular Ca2+ waves is intracellular, specifically the SR Ca2+ stores. In human myocytes, these stores can be visualized (Young Mathur 1999) using the low-affinity Ca2+-dependent fluorescent dye Fluo-3-FF (Fig. 2). Interestingly, the Ca2+ stores... 

The second major group of compounds, the Ca -channel antagonists or Ca + entry blockers, are also a structurally heterogenous group of compounds and appear to function primarily by inhibiting Ca2+ uptake through defined pathways in the plasma membrane. These compounds will form the major focus of this chapter. Special, but not exclusive, emphasis will be placed on their interactions in smooth muscle. 

Slow Calcium Channel Blockers (SCCBs), which are also referred to as calcium entry blockers and even, erroneously, as calcium antagonists, are a number of marketed drugs, several of which have no chemical relationship to the others. They will be discussed in some detail with the anti-anginal drugs (see later). At this point, suffice it to state that their antihypertensive effect is due to their ability to modulate the influx of Ca2+ across the cell membrane of the arterial smooth muscle. This will reduce Ca2+-promoted activation of the cells contractile proteins, leading to vasodilation. 

De la Rosa, L. A., Alfonso, A., Vilarino, N., Vieytes, M.R., Yasumoto, T, and Botana, L.M. 2001a. Maitotoxin-induced calcium entry in human lymphocytes - Modulation by yessotoxin, Ca2-f channel blockers and kinases. Cell Signal 13, 711-716. 

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