Nonmuscle myosin II isoforms interact with sodium channel alpha subunits.

Sodium channels play pivotal roles in health and diseases due to their ability to control cellular excitability. The pore-forming α-subunits (sodium channel alpha subunits) of the voltage-sensitive channels (i.e., Na1.1-1.9) and the nonvoltage-dependent channel (i.e., Na) share a common structural motif and selectivity for sodium ions. We hypothesized that the actin-based nonmuscle myosin II motor proteins, nonmuscle myosin heavy chain-IIA/myh9, and nonmuscle myosin heavy chain-IIB/myh10 might interact with sodium channel alpha subunits to play an important role in their transport, trafficking, and/or function. Immunochemical and electrophysiological assays were conducted using rodent nervous (brain and dorsal root ganglia) tissues and ND7/23 cells coexpressing Na subunits and recombinant myosins. Immunoprecipitation of myh9 and myh10 from rodent brain tissues led to the coimmunoprecipitation of Na, Na1.2, and Na1.3 subunits, but not Na1.1 and Na1.6 subunits, expressed there. Similarly, immunoprecipitation of myh9 and myh10 from rodent dorsal root ganglia tissues led to the coimmunoprecipitation of Na1.7 and Na1.8 subunits, but not Na1.9 subunits, expressed there. The functional implication of one of these interactions was assessed by coexpressing myh10 along with Na1.8 subunits in ND7/23 cells. Myh10 overexpression led to three-fold increase ( P < 0.01) in the current density of Na1.8 channels expressed in ND7/23 cells. Myh10 coexpression also hyperpolarized voltage-dependent activation and steady-state fast inactivation of Na1.8 channels. In addition, coexpression of myh10 reduced ( P < 0.01) the offset of fast inactivation and the amplitude of the ramp currents of Na1.8 channels. These results indicate that nonmuscle myosin heavy chain-IIs interact with sodium channel alpha subunits subunits in an isoform-dependent manner and influence their functional properties.