G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons.

Mechanosensitive cells are essential for organisms to sense the external and internal environments, and a variety of molecules have been implicated as mechanical sensors. Here we report that odorant receptors (ORs), a large family of G protein-coupled receptors, underlie the responses to both chemical and mechanical stimuli in mouse olfactory sensory neurons (OSNs). Genetic ablation of key signaling proteins in odor transduction or disruption of OR-G protein coupling eliminates mechanical responses.

Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors.

Most sensory systems are primarily specialized to detect one sensory modality. Here we report that olfactory sensory neurons (OSNs) in the mammalian nose can detect two distinct modalities transmitted by chemical and mechanical stimuli. As revealed by patch-clamp recordings, many OSNs respond not only to odorants, but also to mechanical stimuli delivered by pressure ejections of odor-free Ringer solution.

Three methionine residues located within the regulator of conductance for K+ (RCK) domains confer oxidative sensitivity to large-conductance Ca2+-activated K+ channels.

Methionine-directed oxidation of the human Slo1 potassium channel (hSlo1) shifts the half-activation voltage by -30 mV and markedly slows channel deactivation at low concentrations of intracellular Ca2+ ([Ca2+]i). We demonstrate here that the contemporaneous mutation of M536, M712 and M739 to leucine renders the channel functionally insensitive to methionine oxidation caused by the oxidant chloramine-T (Ch-T) without altering other functional characteristics. Coexpression with the auxiliary beta1 subunit fails to restore the full oxidative sensitivity to this triple mutant channel.

Expression of a calmodulin-binding KCNQ2 potassium channel fragment modulates neuronal M-current and membrane excitability.

KCNQ2 and KCNQ3 ion channel pore-forming subunits coassemble to form a heteromeric voltage-gated potassium channel that underlies the neuronal M-current. We and others showed that calmodulin (CaM) binds to specific sequence motifs in the C-terminal domain of KCNQ2 and KCNQ3. We also found that a fusion protein containing a KCNQ2 CaM-binding motif, coexpressed with KCNQ2 and KCNQ3, competes with the full-length KCNQ2 channel for CaM binding and thereby decreases KCNQ2/3 current density in heterologous cells.

The beta1 subunit enhances oxidative regulation of large-conductance calcium-activated K+ channels.

Oxidative stress may alter the functions of many proteins including the Slo1 large conductance calcium-activated potassium channel (BKCa). Previous results demonstrated that in the virtual absence of Ca2+, the oxidant chloramine-T (Ch-T), without the involvement of cysteine oxidation, increases the open probability and slows the deactivation of BKCa channels formed by human Slo1 (hSlo1) alpha subunits alone. Because native BKCa channel complexes may include the auxiliary subunit beta1, we investigated whether beta1 influences the oxidative regulation of hSlo1.

Metabolic regulation of potassium channels.

Potassium (K+) channels exist in all three domains of organisms: eubacteria, archaebacteria, and eukaryotes. In higher animals, these membrane proteins participate in a multitude of critical physiological processes, including food and fluid intake, locomotion, stress response, and cognitive functions. Metabolic regulatory factors such as O2, CO2/pH, redox equivalents, glucose/ATP/ADP, hormones, eicosanoids, cell volume, and electrolytes regulate a diverse group of K+ channels to maintain homeostasis.