Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach

Abstract

Du P, Li S, O'Grady G, Cheng LK, Pullan AJ, Chen JD. Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach. Am J Physiol Gastrointest Liver Physiol 297: G672-G680, 2009. First published August 6, 2009 doi:10.1152/ajpgi.00149.2009.-Gastric electrical stimulation (GES) involves the delivery of electrical impulses to the stomach for therapeutic purposes. New GES protocols are needed that are optimized for improved motility outcomes and energy efficiency. In this study, a biophysically based smooth muscle cell (SMC) model was modified on the basis of experimental data and employed in conjunction with experimental studies to define the effects of a large range of GES protocols on individual SMCs. For the validation studies, rat gastric SMCs were isolated and subjected to patch-clamp analysis during stimulation. Experimental results were in satisfactory agreement with simulation results. The results define the effects of a wide range of GES parameters (pulse width, amplitude, and pulse-train frequency) on isolated SMCs. The minimum pulse width required to invoke a supramechanical threshold response from SMCs (defined at Ϫ30 mV) was 65 ms (at 250-pA amplitude). The minimum amplitude required to invoke this threshold was 75 pA (at 1,000-ms pulse width). The amplitude of the invoked response beyond this threshold was proportional to the stimulation amplitude. A highfrequency train of stimuli (40 Hz; 10 ms, 150 pA) could invoke and maintain the SMC plateau phase while requiring 60% less power and accruing ϳ30% less intracellular Ca 2ϩ concentration during the plateau phase than a comparable single-pulse protocol could in a demonstrated example. Validated computational simulations are an effective strategy for efficiently identifying effective minimum-energy GES protocols, and pulse-train protocols may also help to reduce the power consumption of future GES devices.

Multiscale Modeling of Gastrointestinal Electrophysiology and Experimental Validation

“…Animal experiments were only performed at selected combinations to validate the simulated results, thereby significantly reducing the time and resources required. 31 Coupled with experimental data, this study demonstrated the powerful analytical power of mathematical modeling.…”

“…A validated mathematical model offers an alternative virtual medium in which hypotheses regarding normal and abnormal physiology can be exhaustively investigated, and the effects for treatment strategies predicted, without sole reliance on animal and human experimental models. 31 …”

“…In an attempt to improve efficiency in gastric pacing research, the C&B SMC model has been adopted in a recent study to investigate the effects of gastric stimulation protocols, providing an example of its potential applications in in silico hypothesis testing. 31 In that study, the C&B SMC model was parameterized to match the V m response of an initial set of recordings on the V m of rodent gastric SMCs. Because the C&B SMC model carried parameters that represent realistic physical quantities, it was straightforward to update the values of different parameters in the cell model, such as C m , to real experimental conditions.…”

Pulse Width-Dependent Effects of Intestinal Electrical Stimulation for Obesity: Role of Gastrointestinal Motility and Hormones

“…Shortpulse implantable device such as the Enterra® therapy (Medtronic, Minneapolis, MN, USA), employing a shortpulse protocol (14 Hz, 0.1 s on/5.0 s off, 5 mA, pulse width 0.33 ms), has no acute effects on gastric slow waves or gastric emptying, but is capable of improving symptoms of nausea and vomiting via the modulation of vagal afferent pathway [19,20]. However, considering differences in cell capacitance and components of ion channels between neurons and smooth muscle cells, long pulses or trains of long pulses are required to effectively modulate gastrointestinal smooth muscle cell functions [21]. Long-pulse stimulation is composed of repetitive single pulses with a pulse width of 10-600 ms and a stimulation frequency in the vicinity of the physiological frequency of the intestinal slow wave.…”

A Tissue Framework for Simulating the Effects of Gastric Electrical Stimulation andIn VivoValidation

“…In future, computational simulations and high-resolution entrainment mapping may assist in addressing the challenge of improving motility via GES. For example, simulations on biophysically based cell models may help to predict the effects of GES on the membrane potential and calcium influx into SMCs [7], [34]. High-resolution mapping has also recently revealed that gastric dysrhythmias may involve complex focal and reentrant behaviors, similar to those occurring in the heart [23], and the effects of pacing on these complex activities now awaits to be defined via entrainment mapping.…”