Increase In Resting Membrane Potential Research Articles

Characterization of neuromuscular transmission in mice with progressive motoneuronopathy

Progressive motoneuronopathy (PMN) is an autosomal recessive mouse disease, which is characterized by the development of hind limbs paralysis rapidly progressing to the anterior parts of the body, muscular atrophy, respiratory depression, and death at 6-7 postnatal weeks. Here, we recorded the resting membrane potential (RMP), spontaneous miniature endplate potentials (MEPPs), and quantum content of endplate potentials (EPP) at the diaphragm muscle fibers in controls and PMN mice aged 18 to 43 days. In control animals, there was a progressive increase in RMP, MEPP frequency and EPP quantum content, as well as a decrease in mean MEPP amplitude. In PMN mice, the developmental increase in frequency and decrease in the amplitude of MEPPs was practically stopped at the postnatal day 18, whereas RMP increased but only until the age of 31 days and then progressively decreased. The distribution histogram of RMP in PMN mice older than 35 days revealed the existence of two subpopulations of muscle fibers: one showing a denervation-like decrease in RMP and the second, which was matching controls. In addition, EPP quantum content was significantly attenuated in older PMN animals. These results indicate that neurotransmission is severely affected in advanced, but not in early stage of disease, which is apparently due to a partial denervation of the muscles.

VASTUS LATERALIS INTERSTITIAL POTASSIUM RISES WITH TILT IN HUMANS

The myogenic response is the inherent ability of blood vessels to respond to changes in transmural pressure. At the cellular level, the myogenic response is characterized by two important electrophysiological responses to a rise in transmural pressure: 1) an increase in the rate of action potential firing, and 2) a rise in resting membrane potential (RMP). The RMP is determined largely by the K+ concentration gradient across the cell membrane and thus the RMP can be estimated from the Nernst equation. When humans stand, lower extremity transmural pressure increases and it has been suggested that this evokes a myogenic vasoconstrictor response in the legs, which may play an important role in preventing orthostatic hypotension. PURPOSE To examine the effects of head-up tilt on skeletal muscle interstitial K+ concentrations measured in the thigh. METHODS Eight healthy subjects underwent 60 ° head-up tilt for 20 minutes or until they developed orthostatic symptoms. RESULTS Tilt increased (P < 0.05) transmural pressure (92.6 ±6.6 vs. 152.3 ±10.1 mmHg), interstitial K+(5.44 ±0.41 vs. 7.93 ±0.65 mM) and RMP (−86.5 ±1.8 vs. −76.7 ±2.1 mV). In addition, transmural pressure correlated with RMP (r = 0.540, P < 0.05). CONCLUSION These data illustrate that tilt increases transmural pressure, which correlated with the increase in RMP, suggesting that as transmural pressure rises, the myogenic response is engaged.

Involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of porcine coronary artery endothelial cells.

This study investigated the effects of the following adenosine agonists: 5;-ethylcarboxamidoadenosine (NECA), N6-cyclopentyadenosine (CPA) 2-[p-(2-carboxyethyl)]phenylamino-5;N-ethylcarboxamidoadenosine (CGS-21680), and 2-chloroadenosine (CAD) and its antagonist, 4-(2-[7-amino-2-[2-furyl]]1,2,4-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385), a selective A2A adenosine receptor antagonist, and the involvement of the K+ATP and KCa channels on the resting membrane potential (RMP) of confluent monolayers of cultured porcine coronary artery endothelial cells (PCAECs). Adenosine agonists and K+ATP channel openers (pinacidil, cromakalim) hyperpolarized cultured PCAECs. The average RMP was -32.31 +/- 1.2 mV. Adenosine agonists at 10-5 M caused a significant increase in RMP to -65.0 +/- 1.5 mV for CAD (a nonselective adenosine receptor agonist) to -75.9 +/- 1.6 mV for CGS-21680 (a selective A2A receptor agonist) and to -87.0 +/- 3.5 mV for NECA (a nonselective A1/A2A/A2B receptor agonist). Pinacidil and cromakalim at 10 microM increased the membrane potential to -76.2 +/- 1.2 mV and -75.22 +/- 0.12 mV, respectively. The hyperpolarization induced by adenosine receptor agonists and KATP openers was inhibited by an application of the K+ATP channel blocker glibenclamide (10 microM), indicating the involvement of the K+ATP channel in the adenosine-mediated hyperpolarization of PCAECs. Moreover, 1-EB10, a selective opener of the maxi-KCa channel, hyperpolarized PCAECs, and the effect of 1-EB10 was completely blocked by a selective, irreversible blocker of the high conductance KCa (maxi-K) channels (penitrem A), but it only partially blocked the effect of NECA. ZM-241385 has no effect on hyperpolarization elicited by K+ATP and KCa channel openers. However, ZM-241385 significantly blocked the hyperpolarization effect of CAD and CGS-21680. ZM-241385 partially blocked the hyperpolarizing effect of NECA, and a combination of ZM-241385 and penitrem A further blocked the hyperpolarizing effect of NECA. These results further support the involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of PCAECs.

Effect of ouabain on adenosine receptor-mediated hyperpolarization in porcine coronary artery smooth muscle

We investigated the effect of inhibitors of endothelium-derived nitric oxide and sodium-potassium (Na +-K +) pumps on adenosine receptor-mediated hyperpolarization of porcine coronary artery smooth muscle with and without endothelium. The average resting membrane potential (RMP) in porcine coronary artery smooth muscle was −51.5±0.2 and −50.7±0.2 mV, in the presence and absence of endothelium, respectively. Neither ouabain, N-nitro- l-arginine methyl ester ( l-NAME) nor ouabain and l-NAME in combination significantly affected the resting membrane potential in the absence of vasodilator agonists. Adenosine agonists, 2-chloroadenosine and 5′- N-ethylcarboxamidoadenosine at 10 −5 M caused a significant increase in RMP with intact endothelium and caused a smaller but significant increase in RMP in the absence of endothelium. Ouabain (10 −5 M) in the absence of l-NAME significantly reduced hyperpolarization due to 2-chloroadenosine and 5′- N-ethylcarboxamidoadenosine in the presence of endothelium. However, in the absence of endothelium, its inhibitory effect was not significant. When ouabain plus l-NAME (10 −5 M) were given simultaneously, the hyperpolarization caused by adenosine agonists was significantly further attenuated nearly to the RMP level. Attenuation of the response to 2-chloroadenosine and 5′- N-ethylcarboxamidoadenosine by ouabain was not reversed by the nitric oxide precursor, l-arginine (10 −4 M) both in the presence and absence of endothelium. These results suggest that hyperpolarization of vascular smooth muscle of the porcine coronary artery by adenosine agonists is at least partly endothelium dependent and possibly involves the Na +-K + pump and the release of nitric oxide. © 1997 Elsevier Science B.V. All rights reserved.

Role of endothelium in hyperpolarization of coronary smooth muscle by adenosine and its analogues.

We studied the effects of adenosine (AD) and its analogues, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) on membrane potential of porcine coronary artery with an without endothelium, conducting experiments with addition of indomethacin (10(-5) M) to rule out involvement of prostanoids. Average resting membrane potential (RMP) in porcine coronary artery was -51.1 +/- 0.2 and -50.3 +/- 0.2 mV, with and without endothelium, respectively. AD agonists at 10(-5) M caused a significant increase in RMP to -69.5 +/- 0.2 mV for AD, to -82.2 +/- 0.3 mV for CAD, and to -81.2 +/- 0.3 mV for NECA in porcine coronary arteries with intact endothelium. Moreover, AD agonists at 10(-5) M caused a smaller but significant increase in RMP to -54.3 +/- 0.2 mV for AD, -56.1 +/- 0.1 mV for CAD, and -61.1 +/- 0.2 mV for NECA without endothelium. The average RMP for human coronary artery with and without endothelium was -66.1 +/- 0.5 and -64.0 +/- 0.4, respectively. Qualitatively, similar effects of AD and its analogues were observed in two human coronary arteries. The AD receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 10(-5) M) blocked hyperpolarization caused by AD and its analogues with and without endothelium both in porcine and human coronary arteries. The hyperpolarization caused by CAD and NECA in porcine coronary artery was attenuated in part by the nitric oxide (NO) synthase inhibitors N-monomethyl-L-arginine (L-NMMA, 10(-5) M) and N-nitro-L-arginine methylester (L-NAME, 10(-5) M), and the effect of L-NAME was reversed by L-arginine (L-ARG, 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of L-carnitine on action potential of canine papillary muscle during hypoxic perfusion

Under hypoxic (95% N2 + 5% CO2) perfusion, electrophysiological effects of L-carnitine on canine papillary muscles were studied using standard microelectrode techniques. During hypoxic perfusion for 60 min, resting membrane potential (RMP), action potential amplitude (APA) and maximum upstroke velocity of phase 0 were decreased, and action potential duration (APD) and effective refractory period (ERP) were shortened. Application of L-carnitine 25 mM under hypoxic perfusion increased RMP and APA and prolonged APD and ERP significantly. As effects of L-carnitine during hypoxic perfusion might be that of hypertonicity, effects of sucrose of the same tonicity as L-carnitine were studied under hypoxia. Sucrose did not cause significant changes on various parameters of action potential compared with hypoxic perfusion. It was suggested that the increase in RMP, and the prolongation of APD and ERP might be caused by an increase in intracellular ATP content. The findings in this study could be an explanation of possible antiarrhythmic effects of L-carnitine.

Contribution of an electrogenic pump to the modulation of synaptic efficacy

1. 1. A new postsynaptic mechanism for modulating synaptic efficacy is described. 2. 2. The A cluster neurons in the cerebral ganglion of Aplysia have a resting membrane potential (RMP) which increases steadily from −30mV when initially impaled to a final level of −50 to −55 mV. This is close to the Cl − equilibrium potential (E cl − ). 3. 3. This increase in RMP is due to an electrogenic pump, and is blocked by ouabain, cooling and K + free seawater. 4. 4. When initially impaled, both spontaneous and sensory evoked synaptic input to the A neurons consists primarily of IPSPs. With increasing RMP, these first decrease in amplitude and may invert to become depolarizing. 5. 5. Sensory evoked IPSPs have two components. The first is fast and Cl − mediated. The second is slow and K + mediated. 6. 6. During sensory stimulation, the slow component can pull the membrane potential below E cl− causing the fast component to invert (Fig. 3). These inverted IPSPs can summate with other excitatory inputs to produce A neuron firing. 7. 7. Due to the interaction of the electrogenic pump and the two component inhibition, the efficacy of sensory and other synaptic input can be modulated by relatively small changes in membrane potential.

Triiodothyronine effects on some electrogenic properties of frog sartorius.

At 21 degrees C in vitro, 0.2 and 2.0 muM of triiodothyronine (T3) produced an increase in resting membrane potential (RMP) of Rana pipens sartorius when the pH of the external solution was 7.4. The RMP was increased by 2.0 muM T3 in the presence of 10(-4) and 10(-3) M ouabain but not in 10(-3) M of 2,4 dinitrophenol. Small increases in RMP were observed with 2.0 muM T3 in solutions with low external Na. At pH 7.1 0.2 muM T3 produced a small transient increase in RMP. Membrane resistance (Rm) was found to decline gradually during exposure to 0.2 muM at a pH of 7.4. Treatment with 2.0 muM T3 at pH 7.4 was accompanied by a transient reduction in Rm. Similar transient changes in Rm were produced by 0.2 and 2.0 muM T3 at pH of 7.1 T3 reduced membrane resistance in isotonic K2SO4 and tris-buffered Mn (20 mM) solutions indicating that T3 increases potassium permeability. Direct action potentials were studied at pH 7.1. Overshoot, amplitude and rate of rise of the action potential underwent a gradual decrease in the presence of 0.2 muM T3 while thresholds remained unchanged. Thresholds were increased during exposure to 2.0 muM T3 whereas overshoot, amplitude and rate of rise underwent transient decreases followed by a return toward control levels.