Electrical interaction of mechanosensitive fibroblasts and myocytes in the heart

Jiang

American Journal of Physiology-Cell Physiology

et al. 2015

Mittal RK. Inhibitory motor neurons of the esophageal myenteric plexus are mechanosensitive. Am J Physiol Cell Physiol 308: C405-C413, 2015. First published December 24, 2014; doi:10.1152/ajpcell.00159.2014.-Mechanosensitivity of enteric neurons has been reported in the small intestine and colon, but not in the esophagus. Our earlier in vivo studies show that mechanical stretch of the esophagus in the axial direction induces neurally mediated relaxation of the lower esophageal sphincter, possibly through mechanosensitive motor neurons. However, this novel notion that the motor neurons are mechanosensitive has not been examined in isolated esophageal myenteric motor neurons. The goal of our present study was to examine the mechanosensitivity of esophageal motor neurons in primary culture and elucidate the underlying molecular mechanisms. Immmunocytochemical analysis revealed that Ͼ95% cells were positive for the neuronal marker protein gene product 9.5 and that 66% of these cells costained with protein gene product 9.5 and neuronal nitric oxide (NO) synthase. Hypotonic solution induced an increase in the cytoplasm volume in all cells that was independent of extracellular Ca 2ϩ . Hypotonic solution and mechanical stretch induced cytoplasmic free Ca 2ϩ signaling in ϳ65% of neurons in the presence, but not absence, of extracellular Ca 2ϩ . Neurons grown on the elastic membrane responded to mechanical stretch by an increase in neuronal size and Ca 2ϩ signaling simultaneously. Hypotonic stretch-induced cytoplasmic free Ca 2ϩ signaling was not affected by extracellular Mg 2ϩ , 5-nitro-2-(3-phenylpropylamino)benzoic acid, and nifedipine but was attenuated by 2-aminoethoxydiphenyl borate, Gd 3ϩ , and Grammostola mechanotoxin 4, blockers of the stretch-activated ion channels. In ϳ57% of the neurons, hypotonic stretch also induced Ca 2ϩ -dependent cytoplasmic NO production, which was abolished by Grammostola mechanotoxin 4. These results prove that the esophageal inhibitory motor neurons possess a mechanosensitive property and also provide novel insights into the stretch-activated ion channel-Ca 2ϩ -NO signaling pathway in these neurons. neuronal nitric oxide synthase; nitric oxide production; cytoplasmic free calcium; stretch-activated cation channels THE ENTERIC NERVOUS SYSTEM regulates gastrointestinal (GI) functions, such as digestion, absorption, secretion, motility, and sensation (1, 14, 37). The enteric nervous system contains three types of neurons: 1) sensory neurons [intrinsic primary afferent neurons (IPANs)], 2) interneurons, and 3) motor neurons (1, 14). The latter are further subdivided into excitatory and inhibitory motor neurons on the basis of their regulatory functions (1, 15): excitatory motor neurons contain neurotransmitters, such as acetylcholine, substance P, and glutamate (14), and inhibitory motor neurons contain nitric oxide (NO), ATP, and vasoactive intestinal polypeptide (14, 37).Similar to neurons in the rest of the GI tract, neurons in the wall of esophagus also play an important role in the s...

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibitory motor neurons of the esophageal myenteric plexus are mechanosensitive

Jiang

American Journal of Physiology-Cell Physiology

et al. 2015

“…It is recognized that inhibitory impulses, produced by slowly adapting receptors (SARs) in the lungs during inflation [36], play a role in controlling typically autonomic functions such as breathing pattern, airway smooth muscle tone, systemic vascular resistance, and heart rate [37]. Stretch of connective tissue fibroblasts are capable of effecting the membrane potential of nervous tissue [38]. Both hyperpolarization and inhibitory impulses generated by stretch of neural and non-neural tissue of the lungs are the likely agents of autonomic shift during pranayamic breathing.…”

Section: Hypothesismentioning

confidence: 99%

“…It is well documented that hyperpolarization of tissues manifests itself in parasympathetic-like changes [47]. Hyperpolarization is generated during stretch of fibroblasts in tissue surrounding the lungs [38]. Similarly, in some neurons, hyperpolarization current inhibits unsynchronized neuronal input [46] thereby increasing the dominance of synchronized input.…”

Section: Hypothesismentioning

confidence: 99%

Physiology of long pranayamic breathing: Neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system

Jerath¹,

Edry²,

Barnes³

et al. 2006

Medical Hypotheses

368

216

Summary Pranayamic breathing, defined as a manipulation of breath movement, has been shown to contribute to a physiologic response characterized by the presence of decreased oxygen consumption, decreased heart rate, and decreased blood pressure, as well as increased theta wave amplitude in EEG recordings, increased parasympathetic activity accompanied by the experience of alertness and reinvigoration. The mechanism of how pranayamic breathing interacts with the nervous system affecting metabolism and autonomic functions remains to be clearly understood. It is our hypothesis that voluntary slow deep breathing functionally resets the autonomic nervous system through stretchinduced inhibitory signals and hyperpolarization currents propagated through both neural and non-neural tissue which synchronizes neural elements in the heart, lungs, limbic system and cortex. During inspiration, stretching of lung tissue produces inhibitory signals by action of slowly adapting stretch receptors (SARs) and hyperpolarization current by action of fibroblasts. Both inhibitory impulses and hyperpolarization current are known to synchronize neural elements leading to the modulation of the nervous system and decreased metabolic activity indicative of the parasympathetic state. In this paper we propose pranayama's physiologic mechanism through a cellular and systems level perspective, involving both neural and non-neural elements. This theoretical description describes a common physiological mechanism underlying pranayama and elucidate the role of the respiratory and cardiovascular system on modulating the autonomic nervous system. Along with facilitating the design of clinical breathing techniques for the treatment of autonomic nervous system and other disorders, this model will also validate pranayama as a topic requiring more research.

Journal of Applied Physiology

“…Negative pressures and longitudinal stretch of ventricular myocytes increased the open probability of nonselective cation channels, depolarizing cardiac cells, while also prolonging the action potential duration (8,41,49). Additionally, in fibroblast patch clamp experiments, mechanical compression caused depolarization by way of a nonspecific inward cation current, while mechanical stretch led to hyperpolarization (21)(22)(23).…”

mentioning

confidence: 98%

Ultrasound-induced modulation of cardiac rhythm in neonatal rat ventricular cardiomyocytes

Fleischman¹,

Vecchio

Sunny

et al. 2015

Fleischman A, Vecchio C, Sunny Y, Bawiec CR, Lewin PA, Kresh JY, Kohut AR. Ultrasound-induced modulation of cardiac rhythm in neonatal rat ventricular cardiomyocytes. J Appl Physiol 118: 1423-1428, 2015. First published April 9, 2015 doi:10.1152/japplphysiol.00980.2014.-Isolated neonatal rat ventricular cardiomyocytes were used to study the influence of ultrasound on the chronotropic response in a tissue culture model. The beat frequency of the cells, varying from 40 to 90 beats/min, was measured based upon the translocation of the nuclear membrane captured by a high-speed camera. Ultrasound pulses (frequency ϭ 2.5 MHz) were delivered at 300-ms intervals [3.33 Hz pulse repetition frequency (PRF)], in turn corresponding to 200 pulses/min. The intensity of acoustic energy and pulse duration were made variable, 0.02-0.87 W/cm 2 and 1-5 ms, respectively. In 57 of 99 trials, there was a noted average increase in beat frequency of 25% with 8-s exposures to ultrasonic pulses. Applied ultrasound energy with a spatial peak time average acoustic intensity (Ispta) of 0.02 W/cm 2 and pulse duration of 1 ms effectively increased the contraction rate of cardiomyocytes (P Ͻ 0.05). Of the acoustic power tested, the lowest level of acoustic intensity and shortest pulse duration proved most effective at increasing the electrophysiological responsiveness and beat frequency of cardiomyocytes. Determining the optimal conditions for delivery of ultrasound will be essential to developing new models for understanding mechanoelectrical coupling (MEC) and understanding novel nonelectrical pacing modalities for clinical applications.