Considerable progress has been made over the last decade in the understanding of mechanisms responsible for the ontogenetic changes of mammalian intestine. This review presents the current knowledge about the development of intestinal transport function in the context of intestinal mucosa ontogeny. The review predominantly focuses on signals that trigger and/or modulate the developmental changes of intestinal transport. After an overview of the proliferation and differentiation of intestinal mucosa, data about the bidirectional traffic (absorption and secretion) across the developing intestinal epithelium are presented. The largest part of the review is devoted to the description of developmental patterns concerning the absorption of nutrients, ions, water, vitamins, trace elements, and milk-borne biologically active substances. Furthermore, the review examines the development of intestinal secretion that has a variety of functions including maintenance of the fluidity of the intestinal content, lubrication of mucosal surface, and mucosal protection. The age-dependent shifts of absorption and secretion are the subject of integrated regulatory mechanisms, and hence, the input of hormonal, nervous, immune, and dietary signals is reviewed. Finally, the utilization of energy for transport processes in the developing intestine is highlighted, and the interactions between various sources of energy are discussed. The review ends with suggestions concerning possible directions of future research.

The activity of apical membrane Na channels in the rat cortical collecting tubule was studied during manipulation of the animals' mineralocorticoid status in vivo using a low-Na diet or the diuretic furosemide. Tubules were isolated and split open to expose the luminal membrane surface. Induction of Na channel activity was studied in cell-attached patches of the split tubules. No activity was observed with control animals on a normal diet. Channel activity could be induced by putting the animals on the low-Na diet for at least 48 h. The mean number of open channels per patch (NPo) was maximal after 1 wk on low Na. Channels were also induced within 3 h after injection of furosemide (20 mg/kg body wt per d). NPo was maximal 48 h after the first injection. In both cases, increases in NPo were primarily due to increases in the number of channels per patch (N) at a constant open probability (Po). With salt depletion or furosemide injection NPo is a saturable function of aldosterone concentration with half-maximal activity at approximately 8 nM. When animals were salt repleted after 1-2 wk of salt depletion, both plasma aldosterone and NPo fell markedly within 6 h. NPo continued to decrease over the next 14 h, while plasma aldosterone rebounded partially. Channel activity may be dissociated from aldosterone concentrations under conditions of salt repletion.

The circadian clock is an endogenous timekeeper system that controls the daily rhythms of a variety of physiological processes. Accumulating evidence indicates that genetic changes or unhealthy lifestyle can lead to a disruption of circadian homeostasis, which is a risk factor for severe dysfunctions and pathologies including cancer. Cell cycle, proliferation, and cell death are closely intertwined with the circadian clock, and thus disruption of circadian rhythms appears to be linked to cancer development and progression. At the molecular level, the cell cycle machinery and the circadian clocks are controlled by similar mechanisms, including feedback loops of genes and protein products that display periodic activation and repression. Here, we review the circadian rhythmicity of genes associated with the cell cycle, proliferation, and apoptosis, and we highlight the potential connection between these processes, the circadian clock, and neoplastic transformations. Understanding these interconnections might have potential implications for the prevention and therapy of malignant diseases.

High-conductance (maxi) K channels in the apical membrane of rat and rabbit cortical collecting tubules (CCT) were studied using the patch-clamp technique. Principal cells (PC) and intercalated cells (IC) were distinguished with Hoffman modulation optics in split-open tubules. IC were further identified by staining tubules with the fluorescent mitochondrial dye, rhodamine 123. Maxi-K channels were distinguished by their high conductance (greater than 80 pS) and voltage-dependent kinetics. In CCT of rats on a low-Na diet, maxi K channels were observed in 11% of the cell-attached patches on PC and 79% of patches on IC. In rats on a normal diet, the channels were seen in 23 and 79% of patches on PC and IC, respectively. In the rabbit CCT, maxi K channels were observed in 12% (4 of 32) of the patches on PC and 82% (122 of 148) of the patches on IC. The greater abundance of channels in IC was confirmed in rat CCT using the whole-cell clamp technique. Current through the maxi K channels (IK) was measured as the tetraethylammonium (TEA)-sensitive (2.5 mM) outward current in cells equilibrated with 115 mM K and 10(-5) M Ca2+ in the pipette solution. When the cell was clamped to an internal potential of +40 mV, the average IK per cell was -4 +/- 5 pA in PC and 290 +/- 90 pA in IC. Lowering cytoplasmic Ca2+ from 10(-5) M to 10(-7) M reduced IK to 32 +/- 21 pA. Neither single Na channels nor amiloride-sensitive whole-cell currents were seen in IC. Finally, maxi K channels could be activated by pipette suction (10-40 cm H2O) in either cell-attached or inside-out patches on IC from rabbit CCT. This mechanosensitivity was observed even after chelation of free Ca2+ with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the pipette or the bath solutions, implying that stretch activation of these channels was not mediated by increased Ca2+ entry into the cell. The IC maxi K channel may play a role in cell volume regulation or in K secretion during elevation of luminal hydrostatic pressure.