Mammalian members of the classical transient receptor potential channel (TRPC) subfamily (TRPC1-7and Gd 3؉ have opposite effects on whole cell currents through TRPC5 and TRPC6 channels. The potentiation of TRPC4 and TRPC5 by micromolar La 3؉ at extracellular sites close to the pore mouth is a promising tool for identifying the involvement of these isoforms in receptor-operated cation conductances of native cells. Mammalian isoforms of the classical transient receptor potential channel (TRPC)1 subfamily, TRPC1-7, are likely candidates for cation channels mediating phospholipase C-dependent, receptor-operated Ca 2ϩ influx (for reviews, see Refs. 1-5). The properties and activation mechanisms of TRPCs have been studied extensively in heterologous expression systems. By contrast, relatively little information is available on their role in native cells. Two recent studies (6, 7) report that endogenous receptor-stimulated cation currents in vascular smooth muscle cells show properties identical to those described for heterologously expressed TRPC6. Therefore, precise knowledge of the properties of heterologously expressed TRPC channels may be essential to evaluate the involvement of TRPC proteins in receptor-operated cation conductances in native cells.Structurally, TRP channels, like many other cation channels, have been proposed to have six transmembrane segments (S1-S6), intracellular N and C termini, and a pore-forming reentrant loop between S5 and S6. Based on amino acid sequence similarity, the mammalian members of the TRPC subfamily can be subdivided into four groups (4, 8): TRPC1 (group 1), TRPC2 (group 2), TRPC3/6/7 (group 3), and TRPC4/5 (group 4). This subdivision is also supported by functional data. One of the major functional criteria is the mechanism of channel activation. From studies in heterologous expression systems, it is undisputed that receptor-mediated stimulation of phospholipase C is a key event in the activation of all TRPC isoforms. Evidence indicates that currents mediated by TRPC3, TRPC6, or TRPC7 can be activated by diacylglycerol (DAG) independently of protein kinase C (9 -12), although there is some controversy regarding the physiological significance of this stimulation (13). By contrast, TRPC4 and TRPC5 are not activated by DAG, and some evidence indicates that unidentified components of the phospholipase C pathway other than DAG or store depletion activate the channels (14 -16). Other evidence supports a store-dependent activation mechanism (17)(18)(19)(20). TRPC1 has been reported to be a store-dependent channel in some studies (21-23), but doubts have been raised as to whether TRPC1 expression results in the formation of functional plasma membrane channels in mammalian cells (16,24,25). The few data available support a store-operated activation mechanism for TRPC2 (26, 27), but, here again, other evidence suggests that TRPC2 does not form functional channels in all tissues (28). Data from our group, confirmed in several independent laboratories, indicate that several biophysical fe...
Low birth weight is associated with an increased risk of metabolic dysfunction and arterial hypertension in later life. Because of their reduced birth weight twins have been used repeatedly as a natural model to investigate prenatal programming of hypertension. To reveal an early impact of lower nephron endowment on blood pressure, we performed a longitudinal study on lambs from single, twin and triplet pregnancies. The lambs were studied from birth until adulthood, including regular blood analyses, measurements of body weight and blood pressure and post-mortem estimation of glomerular numbers. Relative weight differences between multiples and singletons at birth were -28% for twins and -44% for triplets, respectively. Some lambs showed rapid catch-up growth. Total nephron number of twins and triplets was reduced by 21 and 37% with respect to that of singletons (p < 0.01). However, multiples did not show increased blood pressure within the time frame of this study. No gender-specific effect was observed. Plasma concentrations of creatinine, urea, electrolytes or osmolality also did not differ. Our data indicate that the previously reported postnatal blood pressure differences between sheep multiples and singletons are a time-limited phenomenon. During infancy and adolescence, a reduced nephron number in sheep multiples is neither associated with increased blood pressure nor reflected by plasma parameters.
We report a case of delayed onset Takotsubo cardiomyopathy (TC) in a 69-year-old woman, associated with minor stressors, two weeks after mitral valve replacement. After suffering several minor complications she had fully recovered and her discharge was planned. On the 14th postoperative day she had to be resuscitated due to cardiogenic shock. TC was diagnosed based on reduced ventricular function with apical ballooning and normal coronaries. Treatment with catecholamines and intra-aortic balloon pump led to full recovery. She continues to do well two years after surgery. TC should be considered as a potential cause of delayed ventricular dysfunction in postcardiac surgery patients.
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