Calcium channels play an important role in human health, it is also one of the potential targets waiting for further discovery for application in antifungal drug discovery. Based on years of experience and advanced technology, Creative Biolabs provides a full range of antifungal drug discovery services against calcium channels.
Introduction of Calcium Channels
Calcium channel is an ion channel which shows selective permeability to calcium ions. It is usually divided into two parts: voltage-gated calcium channels and ligand-gated calcium channels.
For illustration, L-type calcium channel blockers are used to treat hypertension by selectively inhibiting these action potentials in the smooth muscle which leads to dilation of blood vessels, which in turn corrects hypertension. T-type calcium channel blockers are used to treat epilepsy for its ability to reduce the neuronal calcium conductance and reduce the likelihood of experiencing epileptic attacks.
Fig1. Subunit structure of voltage gated calcium channels (VGCC). (Gurkoff, 2013)
Calcium Channels as Targets for Antifungal Drug Discovery
Intracellular calcium ions (Ca2+) are important second messengers in all organisms. The calcium homeostasis system, which consists of various calcium channels and pumps, as well as many related proteins and enzymes play important roles in maintaining the optimal Ca2+ concentration in the cytosol and intracellular compartments, such as the vacuole, ER (endoplasmic reticulum) and Golgi apparatus. The increased Ca2+ concentration in yeast and filamentous fungal cells affects a wide range of cellular processes, such as cell cycle progression, sporulation, spore germination, oriented hyphal tip growth, hyphal branching, gene expression, and circadian rhythms. We here take Aspergillus Nidulans and Candida Albicans as examples.
Fig2. Schematic representation of some ion transporters and channels on the fission yeast. (Ramos, 2011)
It has been reported that calcium channels, CchA and MidA, not only can promote fast growth but also have complex roles in regulating conidiation, hyphal polarity and cell wall components in low-calcium environments. The defect of CchA or MidA brings about a sharp reduction in the number of conidiospores, accompanied by abnormal metulae, and undeveloped-phialides at a higher density of inoculum. However, these conidiation defects in mutants can be rescued either by extra-cellular Ca2+ in a calcineurin-dependent way or by osmotic stress in a calcineurin-independent way. It suggests that the high-affinity Ca2+ channel may represent a viable and completely unexplored avenue to reduce conidiation in the Aspergilli.
C. albicans is a common opportunistic pathogen, causing both superficial and life-threatening systemic infections. Calcium signaling is an intriguing aspect in its physiology, attributing to the roles in stress response and morphogenesis. Yvc1 is a member of the transient receptor potential (TRP) family. Its mutant shows a decreased ability of stress response, morphogenesis and attenuated virulence. Yvc1 takes a key role in hyphal polarized growth and re-orientation to host signals. The putative vacuolar calcium channel Yvc1 plays an important role in C. albicans infection and survival in host tissues, which is associated with its pleiotropic effects in several fungal physiological processes, including stress response, morphogenesis, and polarized growth.
With the help of our well-established technologies and experienced scientists, Creative Biolabs is capable to offer and apply the necessary knowledge and technologies for antifungal drug discovery. We provide very flexible options for each specific case. We are happy to make it accessible to all kinds of research and industrial customers. Please do not hesitate to contact us for more information.
References
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