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NEUROREGULATION AND MOTILITY

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

¹Auckland Bioengineering Institute, ³Department of Surgery, and ⁴Department of Engineering Science, The University of Auckland, Auckland, New Zealand; ²Veterans Research and Education Foundation, Oklahoma Veterans Affairs Medical Center, Oklahoma City, Oklahoma; ⁵Department of Surgery, Vanderbilt University, Nashville, Tennessee; and ⁶Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas

Submitted April 24, 2009 ; accepted in final form August 5, 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 –30 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 high-frequency train of stimuli (40 Hz; 10 ms, 150 pA) could invoke and maintain the SMC plateau phase while requiring 60% less power and accruing 30% less intracellular Ca²⁺ 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.

slow wave; gastric electrical stimulation; stimulation protocol; cell model; electrical therapy