Vimentin-positive, c-kit-negative interstitial cells in human and rat uterus: a role in pacemaking?

The mechanism underlying spontaneous pacemaker potential in the uterus is not clearly understood. Several spontaneously active smooth muscles have interstitial cells of Cajal (ICCs) or ICC-like cells. We therefore examined cells from freshly dispersed uterine muscle strips (from pregnant human and rat myometrium) and in situ uterine preparations to determine the cell types present. Both preparations revealed numerous ICC-like cells; they were multipolar, with spider-like projections and enlarged central regions. These cells were readily distinguished from uterine myocytes by their morphology and ultrastructure, i.e., no myofilaments, numerous mitochondria, caveolae, and filaments. In addition, the ICC-like cells were noncontractile. These cells were negative to c-kit, a classic marker for ICCs. They stained positive for the intermediate filament, vimentin, a marker for cells of mesenchymal origin but not differentiated myocytes. The ICC-like cells had a more or less stable resting membrane potential of -58+/-7 mV compared with smooth-muscle cells, -65+/-13 mV, and produced outward current in response to voltage clamp pulses. However, in contrast with uterine myocytes, inward currents were not observed. This is the first description of ICC-like cells in myometrium and their role in the uterus is discussed, as possible inhibitors of intrinsic smooth-muscle activity.

Methicillin-resistant Staphylococcus aureus in dogs and cats: an emerging problem?

There is concern over transmission of methicillin-resistant Staphylococcus aureus (MRSA) between animals and humans. The spread of hospital-acquired and community-acquired MRSA is a major challenge in human medicine. MRSA is rarely isolated from animals but methicillin resistance occurs in staphylococci that are more prevalent in animals. MRSA infections in animals are uncommon and most are associated with exposure to medical hospitals, extensive wounds, prolonged hospitalisation and immunosuppression. The risk to human health appears to be small but a survey of methicillin-resistant staphylococci in animals is required. Thorough investigation of possible zoonotic infections to establish linkage is encouraged. Medical and veterinary staff should appreciate that animals can carry MRSA, cooperate in eliminating infections and monitor animals in medical environments. Veterinary clinics should implement guidelines for dealing with MRSA. Responsible antibiotic use should minimise the spread of antibiotic resistance but a UK monitoring scheme is desirable.

pH regulation and buffering power in gastric smooth muscle.

Intracellular pH can have profound effects on tissue function, but little is known about how pH is regulated, buffered or affects the function of gastric smooth muscle. As the pH of gastric myocytes may alter with pathophysiological disturbance of the gastric lining, or reduction in blood flow to the stomach, these parameters were investigated. Intracellular pH was measured in strips of corpus from rats and guinea-pigs and pH perturbed by the addition of Na butyrate. pH regulation was investigated using pharmacological inhibitors and ionic substitutions. Resting pH was found to be around 7.0, and buffering power relatively high, compared to other muscles in both species. In the guinea-pig amiloride, EIPA and HOE694 prevented pH regulation from an acid load, but amiloride- and EIPA-insensitive pH-regulating mechanisms were found in the rat. The pH-regulatory mechanism present in the rat was also insensitive to DIDS, SITS and removal of external Cl-, but inhibited by Na+ substitution and HOE694. Acidification reduced gastric tone in both species. We conclude that pH alteration will significantly affect gastric contractility, despite a high capacity of the tissue to buffer and regulate pH change. The sensitivity to NHE inhibitors differs between rat and guinea-pig, suggesting that Na+/H+ exchanger isoform expression differs between gastric tissue.

Developmental changes in intracellular pH buffering power in smooth muscle.

Intracellular pH (pHi) is known to modulate contraction. Neonatal tissues can differ from adult tissue in contractile response to stimuli known to alter pHi e.g. hypoxia. Changes of pH are attenuated by buffering, thus any difference in buffering power (beta) between tissues could affect their functional response to pHi perturbation. Similarly the extent to which any extracellular pH (pHo) alteration is transmitted into a pHi change will also influence function. We have therefore determined the intrinsic beta and effect of pHo change on pHi in neonatal and adult ureteric, uterine and gastric smooth muscles using the pH-sensitive fluorophore carboxy-SNARF. beta was found to be similar in the three adult tissues, but there were significant differences between neonatal tissues. In contrast, we found little difference in the amount of pHi change produced by pHo change between neonatal and adult tissues from the same smooth muscle, but a difference between smooth muscles. These data highlight significant differences between smooth muscles and their developmental state, which may contribute to different degrees of protection when pH is perturbed.