Importance Of Membrane Potential Research Articles

The FlatwormMacrostomum lignanoIs a Powerful Model Organism for Ion Channel and Stem Cell Research

Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. Here we introduce the flatworm Macrostomum lignano as a versatile model organism for addressing these topics. We discuss biological and experimental properties of M. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration in M. lignano.

Impaired β-Adrenoceptor-Mediated Hyperpolarization in Resistance Arteries from Prehypertensive Shr

P49 Stimulation of vascularβ-adrenoceptors leads to smooth muscle hyperpolarization, presumably through theβ-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K + -channels (KATP) signaling cascade, which has been shown to play an important role in the sympathetic control of membrane potential. Impairedβ-adrenoceptor-mediated hyperpolarization has been reported in established stage of hypertension in rat models. However, it is not known whether such an abnormality exists in prehypertensive stage. To clarify this point, we comparedβ-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Systolic blood pressure did not differ between these rats (137.5±4.3 vs. 138.1±2.3mmHg; P=ns, n=10). Isoproterenol-induced hyperpolarization was significantly less in prehypertensive SHR than in WKY (10 -7 mol/L; -4.6±0.6 vs. -7.8±0.8mV; P<0.01, 10 -6 mol/L; -7.8±0.5 vs. -9.8±0.6mV; P<0.05; n=9 in each). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR (10 -6 mol/L; -2.1±0.9 vs. -4.5±0.6mV; P<0.05; n=6 in each). On the other hand, hyperpolarization to forskolin, a direct activator of adenylate cyclase, and that to levcromakalim, a KATP opener, were comparable in both groups. These findings suggest thatβ-adrenoceptor-mediated hyperpolarization is defective already in prehypertensive SHR, presumably due to an abnormality at the level of Gs protein. In view of the importance of membrane potential in the control of vascular tone, such a defect may play a pathogenic role in genetic hypertension through an increase in vascular resistance.

Excitation of vascular muscles by norepinephrine.

The mechanism by which norepinephrine causes excitation of vascular muscle is a concept that has undergone considerable change in the last several years. Although the excitation step is absolutely fundamental to understanding constriction and dilation of arteries, several aspects of the hypothesis are not well understood and have recently been controversial. The earliest view of the excitation process was that action potentials propagate uniformly along the arterial wall, just as fast skeletal muscle, and was disproved early in recording of electrical events from blood vessel walls. The view that then emerged was that membrane potential acts as an analog signal controlling contraction through graded depolarization which, unlike that found in fast skeletal or cardiac muscle, could be maintained for minutes or even hours. This concept of graded depolarization and graded contraction has served as the best model of the vascular muscle excitation process for about 20 years. However, questions have been raised about the importance of membrane potential as a control mechanism because of reports of noncorrelations between membrane potential and tension. The controversy centers around two alternate proposals for the excitatory action of norepinephrine. The proposal of the noncorrelation group is that mechanisms other than membrane potential exert the major control over contraction, perhaps with spatially specialized receptors such that only those areas near nerve endings would cause depolarization as part of the event initiating contraction. On the other hand, the proposal by the strong correlation group would be that membrane potential is the dominant control mechanism. Where experiments have been carried out to specifically test the existence of a noncorrelation between membrane potential and contraction, no failure of correlation was found. The fundamental problem in each instance of a noncorrelation appears to be the attempt to record tension from one part of an artery and membrane potential from another part, which is assumed to behave as an electrically and mechanically homogeneous unit. However, direct measurements of localized areas of the blood vessel wall show such an assumption to be unjustified. In fact, cell-to-cell conduction of an electrical signal to synchronize the blood vessel could not be supported in experiments using refined intracellular and extracellular recording methods.+2