I Ks channels are composed of I sK and KvLQT1 subunits and underly the slowly activating, voltagedependent I Ks conductance in heart. Although it appears clear that the I sK protein aects both the biophysical properties and regulation of I Ks channels, its role in channel pharmacology is unclear. In the present study we demonstrate that KvLQT1 homopolymeric K + channels are inhibited by the I Ks blockers 293B, azimilide and 17-b-oestradiol. However, I Ks channels induced by the coexpression of I sK and KvLQT1 subunits have a 6 ± 100 fold higher anity for these blockers. Moreover, the I Ks activators mefenamic acid and DIDS had little eect on KvLQT1 homopolymeric channels, although they dramatically enhanced steady-state currents through heteropolymeric I Ks channels by arresting them in an open state. In summary, the I sK protein modulates the eects of both blockers and activators of I Ks channels. This ®nding is important for the action and speci®city of these drugs as I sK protein expression in heart and other tissues is regulated during development and by hormones.

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1. The rate of entry into the plasma of stearic acid in fed and starved non-pregnant sheep and of palmitic acid in fed and starved pregnant sheep has been measured by a continuous-infusion isotope-dilution method. 2. In non-pregnant sheep the entry rate of stearic acid rose from 0.38mg./min./kg. when fed to 0.69mg./min./kg. after 72hr. starvation. In pregnant sheep, the entry rate of palmitic acid rose from 0.55mg./min./kg. when fed to 0.64mg./min./kg. on starvation. 3. The entry rates of palmitic acid and stearic acid are related to their respective plasma concentrations. 4. At a given plasma concentration the entry rate of palmitic acid in pregnant sheep was greater than that of stearic acid in non-pregnant sheep. 5. There was no detectable conversion of palmitate or stearate into other plasma long-chain fatty acids. There was negligible incorporation of fatty acids into other plasma lipids with the exception of the plasma triglycerides of fed pregnant sheep. 6. Up to 12% of expired carbon dioxide was derived from palmitic acid or stearic acid. The high rate of oxidation of plasma palmitic acid in fed pregnant sheep is noteworthy.