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Ca2+ sensitization has been postulated to contribute to the myogenic contraction of resistance arteries evoked by elevation of transmural pressure. However, the biochemical evidence of pressure-induced increases in phosphorylated myosin light chain phosphatase (MLCP) targeting subunit 1 (MYPT1) and/or 17 kDa protein kinase C (PKC)-potentiated protein phosphatase 1 inhibitor protein (CPI-17) required to sustain this view is not currently available. Here, we determined whether Ca

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Helical rosette nanotubes (RNTs) are obtained through the self-assembly of the GwedgeC motif, a self-complementary DNA base analogue featuring the complementary hydrogen bonding arrays of both guanine and cytosine. The first step of this process is the formation of a 6-membered supermacrocycle (rosette) maintained by 18 hydrogen bonds, which then self-organizes into a helical stack defining a supramolecular sextuple helix whose chirality and three-dimensional organization arise from the chirality, chemical structure, and conformational organization of the GwedgeC motif. Because a chiral GwedgeC motif is predisposed to express itself asymmetrically upon self-assembly, there is a natural tendency for it to form one chiral RNT over its mirror image. Here we describe the synthesis and characterization of a chiral GwedgeC motif that self-assembles into helical RNTs in methanol, but undergoes mirror image supramolecular chirality inversion upon the addition of very small amounts of water (<1% v/v). Extensive physical and computational studies established that the mirror-image RNTs obtained, referred to as chiromers, result from thermodynamic (in water) and kinetic (in methanol) self-assembly processes involving two conformational isomers of the parent GwedgeC motif. Although derived from conformational states, the chiromers are thermodynamically stable supramolecular species, they display dominant/recessive behavior, they memorize and amplify their chirality in an achiral environment, they change their chirality in response to solvent and temperature, and they catalytically transfer their chirality. On the basis of these studies, a detailed mechanism for supramolecular chirality inversion triggered by specific molecular interactions between water molecules and the GwedgeC motif is proposed.

Abstract-Inhibition of vascular smooth muscle (VSM) delayed rectifier K ϩ channels (K DR ) by 4-aminopyridine (4-AP; 200 mol/L) or correolide (1 mol/L), a selective inhibitor of Kv1 channels, enhanced myogenic contraction of rat mesenteric arteries (RMAs) in response to increases in intraluminal pressure. The molecular identity of K DR of RMA myocytes was characterized using RT-PCR, real-time PCR, and immunocytochemistry. Transcripts encoding the pore-forming Kv␣ subunits, Kv1.2, Kv1.4, Kv1.5, and Kv1.6, were identified and confirmed at the protein level with subunit-specific antibodies. Kv␤ transcript (␤1.1, ␤1.2, ␤1.3, and ␤2.1) expression was also identified. Kv1.5 message was Ϸ2-fold more abundant than that for Kv1.2 and Kv1.6. Transcripts encoding these three Kv1␣ subunits were Ϸ2-fold more abundant in 1st/2nd order conduit compared with 4th order resistance RMAs, and Kv␤1 was 8-fold higher than Kv␤2 message. RMA K DR activated positive to Ϫ50 mV, exhibited incomplete inactivation, and were inhibited by 4-AP and correolide. However, neither ␣-dendrotoxin or -dendrotoxin affected RMA K DR , implicating the presence of Kv1.5 in all channels and the absence of Kv1.1, respectively. Currents mediated by channels because of coexpression of Kv1.2, Kv1.5, Kv1.6, and Kv␤1.2 in human embryonic kidney 293 cells had biophysical and pharmacological properties similar to those of RMA K DR . It is concluded that K DR channels composed of heteromultimers of Kv1 subunits play a critical role in myogenic control of arterial diameter. Key Words: delayed rectifier potassium channel Ⅲ KCNA Ⅲ vascular smooth muscle Ⅲ myogenic contraction Ⅲ arterial diameter T he ability of small resistance arteries to develop myogenic tone in response to elevations in intraluminal (or transmural) pressure is an essential autoregulatory mechanism and an important determinant of peripheral vascular resistance, regional blood flow, and blood pressure. Pressureinduced depolarization of vascular smooth muscle (VSM) leading to increased intracellular Ca 2ϩ ([Ca 2ϩ ] i ) via voltagedependent activation of Ca 2ϩ channels is required for myogenic tone development. 1,2 However, the depolarization does not evoke regenerative action potentials, rather incremental changes in diameter are achieved by graded, steady-state depolarizations. 3 Our understanding of the ionic basis of this precise control of myogenic depolarization is incomplete.Increased intraluminal pressure is thought to activate nonselective cation or Cl Ϫ channels of VSM cells, 2 with the level of depolarization attributable to these channels precisely controlled by an activation of VSM K ϩ channels. 3 Compelling evidence for a contribution of large Ca 2ϩ -activated K ϩ channels (BK Ca ) to this feedback control comes from studies using specific inhibitors (eg, iberiotoxin) and transgenic mice lacking the BK Ca modulatory ␤1 subunit. 4 However, whether other channels are also involved in controlling myogenic depolarization in VSM is not clear.Voltage-gated delayed rectifier channels (K DR ) ...

The performance of physical work in the heat can be affected for better or worse by a variety of factors, the most important being physical fitness and acclimatization, nutritional state, clothing and drugs. This paper deals with the effects of water, salt and glucose, with principal emphasis upon the attainment of the best possible performance. The effects of water soluble vitamins will be mentioned briefly. The present material will be restricted in two ways. First,. attention will be confined to performance of fixed tasks by fully acclimatized men working intermittently in moist or in dry heat. Therefore, the results are applicable to steel workers, miners and soldiers in tlhe desert, all of whom usually do a day's work in the heat and spend the rest of the time in cooler surroundings. Second, we shall consider only the immediate hour to hour effects of the above dietary factors upon men n-hose overall daily intake was always adequate in water, salt, carbohydrate and vitamins. There will be no consideration of prolonged deficiency or excess from day to day. METHODS. Experiments were performed in the late fall or winter in a heated room under hot dry (100 F., 30 per cent relative humidity) and hot moist conditions (95 F. and 90 F., 83 per cent relative humidity). Six healthy young men, fully acclimatized as judged by the criteria of Robinson and colleagues (1943), marched at least three times a week at 3.5 m.p.h. up grades which will be specified in the tables. Depending upon the severity of the temperature and humidity, which were const,ant in individual series of experiments, they marched anywhere from one to six hours with a ten minute rest in each hour. Certain measurements were made periodically in every experiment. These were: a, environmental temperature and humidity with a sling psychrometer; 6, pulse rate by palpation; c, rectal t#emperature with a calibrated clinical thermometer; d, sweating by net change in nude body weight. Other measurements were made in some, but not all, experiments. These were: e, respiratory exchange by collection of expired air in a Tissot gasometer after the subject was in a steady state, analysis for carbon dioxide and oxygen with the Haldane apparatus, and calculation of the oxygen consumption by standard procedures (Haldane, 1934; Peters and Van Slyke, 1932); f, protein by the micro Kjeldahl method of Ma

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