We conducted a kinetic analysis of the voltage dependence of macroscopic inactivation (τ fast , τ slow ), closed-state inactivation (τ closed,inact ), recovery (τ rec ), activation (τ act ), and deactivation (τ deact ) of Kv4.3 channels expressed alone in Xenopus oocytes and in the presence of the calciumbinding ancillary subunits KChIP2b and KChIP2d. We demonstrate that for all expression conditions, τ rec , τ closed,inact and τ fast are components of closed-state inactivation transitions. The values of τ closed,inact and τ fast monotonically merge from −30 to −20 mV while the values of τ closed,inact and τ rec approach each other from −60 to −50 mV. These data generate classic bell-shaped time-constant-potential curves. With the KChIPs, these curves are distinct from that of Kv4.3 expressed alone due to acceleration of τ rec and slowing of τ closed,inact and τ fast . Myocytes isolated from subepicardial and subendocardial surfaces of the free wall of the left ventricle (LV) display significant differences in action potential amplitude, plateau duration, and frequency-dependent characteristics (Antzelevitch & Dumaine, 2002;Carmeliet & Vereecke, 2002). Nonetheless, the action potentials of both myocyte types display a characteristic early repolarization ('phase 1' or 'notch') occurring immediately after the upstroke and preceding the plateau. This early repolarization is primarily governed by a rapidly activating and inactivating K + current phenotype designated 'I to Archer & Rusch, 2001;Oudit et al. 2001;Nerbonne, 2002). Since the kinetics of I to closely overlap those of the L-type calcium current, it is not only a significant regulator of ventricular repolarization but also the excitation-contraction coupling process, and thus overall cardiac performance (Heppner et al. 1966;Morad & Trautwein, 1968;Giles & van Ginnecken, 1985;Campbell et al. 1995;Bers, 2001;Carmeliet & Vereecke, 2002;Sah et al. 2003).Prominent I to phenotypes have been recorded in ventricular myocytes of many species, including mice, rats, rabbits, cows, cats, dogs, ferrets and humans Oudit et al. 2001;Carmeliet & Vereecke, 2002;Nerbonne, 2002;Sah et al. 2003). The designation 'I to ' has thus become synonymous with any rapidly activating and inactivating K + current present in a given ventricular myocyte. However, depending upon both species and anatomical region, there may be at least two functionally distinct I to phenotypes, 'I to,slow ' and 'I to,fast ' . I to,slow displays very slow kinetics of recovery from inactivation (time constants on the order of seconds) with marked cumulative inactivation, is not blocked by Heteropoda toxin, and is likely generated by Kv1.4 α subunits (Nabauer et al. 1996;Brahmajothi et al. 1999;Nerbonne, 2002). I to,slow is prominent in ferret and human LV subendocardial myocytes, and appears to be the predominant I to phenotype in rabbit ventricle (Giles & Imaizumi, 1988;Nabauer et al. 1996;Brahmajothi et al. 1999). In contrast, I to,fast displays rapid recovery kinetics (time constants on the order of tens ...

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Noble gases have played a key role in our understanding of the origin of Earth's volatiles, mantle structure, and long-term degassing of the mantle. Here we synthesize new insights into these topics gained from high-precision noble gas data. Our analysis reveals new constraints on the origin of the terrestrial atmosphere, the presence of nebular neon but chondritic krypton and xenon in the mantle, and a memory of multiple giant impacts during accretion. Furthermore, the reservoir supplying primordial noble gases to plumes appears to be distinct from the mid-ocean ridge basalt (MORB) reservoir since at least 4.45 Ga. While differences between the MORB mantle and plume mantle cannot be explained solely by recycling of atmospheric volatiles, injection and incorporation of atmospheric-derived noble gases into both mantle reservoirs occurred over Earth history. In the MORB mantle, the atmospheric-derived noble gases are observed to be heterogeneously distributed, reflecting inefficient mixing even within the vigorously convecting MORB mantle. ▪ Primordial noble gases in the atmosphere were largely derived from planetesimals delivered after the Moon-forming giant impact. ▪ Heterogeneities dating back to Earth's accretion are preserved in the present-day mantle. ▪ Mid-ocean ridge basalts and plume xenon isotopic ratios cannot be related by differential degassing or differential incorporation of recycled atmospheric volatiles. ▪ Differences in mid-ocean ridge basalts and plume radiogenic helium, neon, and argon ratios can be explained through the lens of differential long-term degassing.