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Cover Image
Cover Image
Cover picture: Ethanol increases (left) and decreases (right) BK (cbv1+wt β2) channel activity at submicromolar and high micromolar calcium, respectively. These responses are shared by cbv1±β1, β2-IR, β3, and β4. At 3–20 μM calcium, however, cbv1±β3/β4 are activated by ethanol, whereas cbv1+β1/wt β2/β2-IR are inhibited. Using the Horrigan–Aldrich allosteric model, our study reveals the gating mechanisms underlying the differential responses of β subunit–containing BK channels to ethanol (see Research Article by Kuntamallappanavar and Dopico, 419–440).
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Article
Independent activation of ion conduction pores in the double-barreled calcium-activated chloride channel TMEM16A
The TMEM16 family contains dimeric membrane proteins activated by intracellular Ca2+. Realizing that lipid scramblase family members contain two independently activated subunits, Lim et al. use concatenated TMEM16A subunits to show that ion channel members contain two independently activated pores.
Independent activation of distinct pores in dimeric TMEM16A channels
TMEM16 lipid scramblases are formed from two identical subunits, but the pore architecture of TMEM16 channels remains unclear. Jeng et al. use tandem dimers of TMEM16A subunits with different mutations and show that each subunit comprises an independent pore and contains more than one Ca2+-binding site.
The Hv1 proton channel responds to mechanical stimuli
Hv1 is a voltage-gated proton channel that is composed of two voltage-sensing domains, each of which is permeable to protons. Pathak et al. find that these voltage-sensing domains are mechanosensitive and that membrane stretch results in a long-lived facilitation of Hv1 activation.
Alcohol modulation of BK channel gating depends on β subunit composition
Large conductance K+ channels of the slo1 family are gated by Ca2+ and voltage and either inhibited or potentiated by ethanol. Kuntamallappanavar and Dopico analyze the effects of ethanol in detail and find that the absence or presence of β subunits leads to differential modification of channel gating parameters by intoxicating levels of ethanol.
