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Calcium Homeostasis Modulators

Calcium homeostasis has major roles in different extra and intra cellular processes and is therefore crucial for cell physiology. CALHM channel gating is regulated allosterically by both voltage and Ca2+ concentration. Low concentrations of Ca2+ and depolarization cause channel activation. The molecular basis for voltage-dependent gating remains unknown. CALHM3 channels do not have canonical voltage sensors as found in other channels. CALHM channels poorly discriminate cations and anions enabling signaling molecules such as Ca2+ and ATP to permeate to its pore. This suggests a non-discriminatory ion selectivity filter or a wide ion conduction pore. Recent studies have shown that it is the latter and not the former that accounts for weak ion selectivity.

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