Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins - PubMed (original) (raw)

CALHM1 is a poorly selective ion channel. A, divalent-free voltage protocol. B, divalent voltage protocol. C, representative families of current traces from CALHM1-expressing (red) and control (blue) oocytes in response to the divalent-free voltage protocol shown in A and described under “Experimental Procedures.” Oocytes were bathed in a solution containing 100 m

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NaCl, 10 m

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HEPES, 0.5 m

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EGTA, 0.5 m

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EDTA, pH 7.3. D, representative families of current traces from CALHM1-expressing (red) and control (blue) oocytes in response to the divalent voltage protocol shown in B and described under “Experimental Procedures.” Oocytes were bathed in a solution containing 100 m

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NaCl, 2 m

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CaCl2, 10 m

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HEPES, pH 7.3. E, normalized instantaneous _I_-V curves from representative CALHM1-expressing oocyte. Increasing [NaCl]o depolarized _E_rev. The solid lines are linear fits. F, permeabilities of K+, Cl−, and Ca2+ relative to Na+ were determined by plotting Erev from _E_rev versus [NaCl]o in the absence (red) or presence (black) of extracellular Ca2+, and the solid lines were calculated by fitting the data with either the Goldman-Hodgkin-Katz constant field equation (Equation 1) or the extended constant field equation (Equations 2–5), respectively. G, normalized instantaneous _I_-V curves from representative CALHM1-expressing oocytes bathed in 100 m

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monovalent cation solutions. Shifts in _E_rev enabled calculation of relative permeabilities. Solid lines, linear fits. H, normalized instantaneous _I_-V curves from representative CALHM1-expressing oocytes bathed in various [Ca2+]o. Increasing [Ca2+]o depolarized _E_rev. Solid lines, linear fits. I, relative permeabilities of divalent cations (M2+) were determined by plotting _E_rev from H versus bath M2+ activity, and the solid lines were derived from fitting the data with the constant field equation (Equations 2–5). J, pharmacology of CALHM1 currents. Averaged, normalized currents (mean ± S.E.) are shown for 1 m

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probenecid (green, n = 4), 30 μ

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mefloquine (red, n = 4), and 200 μ

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quinine (blue, n = 4). Black line, currents recorded in control oocyte injected only with Cx38 antisense oligonucleotide, normalized to the average CALHM1 currents (7.8 ± 1.1 μA, n = 12) from the same batch of oocytes.