Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.

This paper describes the design, implementation, and field testing of an infrastructureless system for autonomous tramming (or hauling) of a center-articulated underground mining vehicle. Such vehicles are ubiquitous in underground mining, and effective automation of their tramming function has been a sought-after technology for more than a decade. This paper reports on the successful development of a fast, reliable, and robust "autotramming" technology that does not require the installation of fixed infrastructure. Included are descriptions of the chosen control architecture, map-based localization technique, and the results of integration and field testing. C 2008 Wiley Periodicals, Inc.