Search

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca2+- activated K+channels (KCa2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca2+-dependent. Further, the Ca2+dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.

Fourteen late juvenile monkeys were subjected to a single 30-min episodes of markedhypotension using an infusion of trimethaphan. Afterward, blood pressure was rapidly restored to and maintained at preinsult levels with an intravenous drip of phenylephrine (.02 mg/ml). The respiratory gas tensions and pH of the arterial blood weremaintained within normal limits at all times. During the 30-min episodes, the cortical electrical impedence increased by a mean of 27% while the EEG frequencies and amplitudes decreased by 47 and 30%, respectively. The impedance and EEG activity generally altered at the same time but inversely to one another, although, on restoration of blood pressure, the impedance recovered within minutes while the EEG activity returned to normal only after 1 h. The impedance values and EEG activity of those animals that eventually died began to diverge significantly from the values of theanimals that were to survive at about 2.5 h after restoration of blood pressure.