Origin and propagation of individual slow waves along the intact feline small intestine

First published online on December 21, 2007.
Experimental Physiology (2007)
DOI: 10.1113/expphysiol.2007.039180
Wim J Lammers 1* Betty Stephen 1
1 United Arab Emirates University
* To whom correspondence should be addressed. E-mail: wlammers@uaeu.ac.ae.
The pattern of propagation of slow waves in the small intestine is not clear. Specifically, it is not known whether propagation is determined by a single dominant ICC-MP pacemaker unit or whether there are multiple active pacemakers. To determine this pattern of propagation, waveforms were recorded simultaneously from 240 electrodes distributed along the whole length of the intact isolated feline small intestine. After the experiments, the propagation patterns of successive individual slow waves were analyzed.In the intact small intestine, there was only a single slow wave pacemaker unit active and this was located at or 6-10 cm from the pyloric junction. From this site, slow waves propagated in the aboral direction at gradually decreasing velocities. The majority of slow waves (73%) reached the ileocaecal junction while the remainder waves were blocked. Ligation at 1-4 locations led to a) decrease in the distal frequencies, b) disappearance of distal propagation blocks, c) increase in velocities, d) emergence of multiple and unstable pacemaker sites and, e) propagation from these sites in the aboral and oral directions. In conclusion, in the quiescent small intestine, a single pacemaker unit dominates the organ with occasional propagation blocks of the slow waves thereby producing the well-known frequency gradient.

Genetically altered animal models for Mas and Angiotensin-(1-7)

First published online on December 21, 2007.
Experimental Physiology (2007)
DOI: 10.1113/expphysiol.2007.040345
Natalia Alenina 1, Ping Xu 1, Brit Rentzsch 1, Eugene L Patkin 2, Michael Bader 3*
1 MDC
2 Institute for Cytology, RAMS
3 Max-Delbrück-Centrum für Molekulare Medi
* To whom correspondence should be addressed. E-mail: mbader@mdc-berlin.de.
Mas is the receptor for angiotensin-(1-7) and involved in cardiovascular and neuronal regulation, in which also the heptapeptide plays a major role. Mas-deficient mice were previously generated by them and their characterization showed that Mas has important functions in behaviour and cardiovascular regulation. These mice exhibit increased anxiety but despite an enhanced long-term potentiation in the hippocampus are not performing better in learning paradigms. When Mas-deficient mice are backcrossed to the FVB/N genetic background a cardiovascular phenotype is uncovered: the backcrossed animals become hypertensive. Concordant with their detection by fluorescent in-situ hybridization of Mas-mRNA in mouse endothelium, this phenotype is caused by endothelial dysfunction based on a dysbalance between nitric oxide and reactive oxygen species in the vessel wall. In agreement with these data, transgenic SHR-SP-rats overexpressing ACE2 in the vessel wall exhibit reduced blood pressure due to an improved endothelial function. Moreover, angiotensin-(1-7) overexpression in transgenic rats has cardioprotective and hemodynamic affects. In conclusion, the angiotensin-(1-7) / Mas axis has important functional implications in vascular regulation and blood pressure control in particular in pathophysiological situations.

Transformation of adult rat cardiac myocytes in primary culture

First published online on December 21, 2007.
Experimental Physiology (2007)
DOI: 10.1113/expphysiol.2007.040659
Tamas Banyasz 1*, Ilya Lozinskiy 2, Charles E Payne 2, Stephanie Edelmann 2, Byron Norton 2, Biyi Chen 2, Ye Chen-Izu 2, Leighton Izu 2, William C Balke 2
1 University of Debrecen
2 University of Kentucky
* To whom correspondence should be addressed. E-mail: tbany2@email.uky.edu.
they characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, ICa,L, IK1, cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of five days long culture. they also analyzed the health of the myocytes using an apoptotic/necrotic viability assay. The data shows that myocytes undergo profound morphological and functional changes during culture. theyobserved a progressive reduction in the cell area (2502±70 µm2, day 0, to 1432±50 µm2, day 5), T-tubule density, systolic shortening (0.11±0.02µm to 0.05±0.01µm) and amplitude of calcium transients (1.54±0.19 to 0.67±0.19) over five days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first two days but diminished afterwards. Cell capacitance (156±8pF to 105±11pF) and membrane currents were also reduced (ICa,L: 3.98pA±0.39A/pF to 2.12±0.37pA/pF, I K1: 34.34p±2.31A/pF to 18.00±5.97pA/pF). they observed progressive depolarization of the resting membrane potential during culture (77.3±2.5mV to 34.2±5.9mV) and consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but rather an adaptation to the culturing conditions over time.

Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat

First published online on December 21, 2007.
Experimental Physiology (2007)
DOI: 10.1113/expphysiol.2007.040055
Frank Christopher Howarth 1*, Michael Jacobson 2, Mohamed Shafiullah 1, Ernest Adeghate 1
1 United Arab Emirates University
2 Higher Colleges of Technology
* To whom correspondence should be addressed. E-mail: chris.howarth@uaeu.ac.ae.
In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ) iV induced diabetic rat these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram (ECG) that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar ¡V Lead II configuration. ECG, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data was acquired for 2 weeks each month. Non-fasting blood glucose and body weight were measured periodically and a glucose tolerance test was performed during the last month of the experiment. Growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased in GK rats compared to age-matched controls. HR was significantly lower in GK rats compared to controls at 2, 7 and 15 months of age. At 2 months of age HR was 316±6 beats per minute (BPM) in GK rats compared to 370±7 BPM in controls. There was a progressive age-dependent decline in HRV in control rats however, HRV in GK rats did not alter significantly with age. HRV was significantly reduced in GK rats compared to controls at 2 and 7 months. At 2 months of age HRV was 28±2 BPM in GK rats compared to 38±3 BPM in controls. Reduced HR and HRV and changes in HRV with time in GK rats compared to age-matched controls may be associated with a progressively developing autonomic neuropathy.