In the molecular-level world of ion channels – passageways through membranes that carry signals in a cell’s environment and allow it to respond – researchers have debated about the role of a small piece of the channel called a linker, says computational biophysicist Jianhan Chen.
The linker communicates between the pore and its environment-sensing apparatus, and knowing its function – whether it’s inert or plays an active sensing role – has been unclear. But it might lead to a new target for drugs and treatment in conditions such as hypertension, autism, epilepsy, stroke and asthma, he adds. Now, Chen and colleagues at Washington University report in eLife that their experiments have revealed “the first direct example of how non-specific membrane interactions of a covalent linker can regulate the activation of a biological ion channel.”
Specifically, Chen and co-first authors Mahdieh Yazdani and Zhiguang Jia at UMass Chemistry, with co-first author Guohui Zhang, Jingyi Shi and Jianmin Cui at Washington University, studied a pore called the large-conductance potassium (BK) channel. It is important in muscle and neuron function and is controlled by calcium concentration via a calcium-sensing domain. It is also controlled by electrical potential through a voltage-sensing domain. Either way, it opens and closes like a gate – “a really common architecture in transmembrane receptors and channels,” Chen says.