The vascular myogenic response refers to the acute reaction of a blood vessel to a change in transmural pressure. This response is critically important for the development of resting vascular tone, upon which other control mechanisms exert vasodilator and vasoconstrictor influences. The purpose of this review is to summarize and synthesize information regarding the cellular mechanism(s) underlying the myogenic response in blood vessels, with particular emphasis on arterioles. When necessary, experiments performed on larger blood vessels, visceral smooth muscle, and even striated muscle are cited. Mechanical aspects of myogenic behavior are discussed first, followed by electromechanical coupling mechanisms. Next, mechanotransduction by membrane-bound enzymes and involvement of second messengers, including calcium, are discussed. After this, the roles of the extracellular matrix, integrins, and the smooth muscle cytoskeleton are reviewed, with emphasis on short-term signaling mechanisms. Finally, suggestions are offered for possible future studies.

https://www.physiology.org/doi/pdf/10.1152/physrev.1999.79.2.387

Signaling mechanisms underlying the vascular myogenic response

The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of refractoriness until the next...

Molecular Physiology of Cardiac Repolarization

Janmey, Paul A. The Cytoskeleton and Cell Signaling: Component Localization and Mechanical Coupling. Physiol. Rev. 78: 763–781, 1998. — The three-dimensional intracellular network formed by the fil...

The Cytoskeleton and Cell Signaling: Component Localization and Mechanical Coupling

The aim of this review is to provide basic information on the electrophysiological changes during acute ischemia and reperfusion from the level of ion channels up to the level of multicellular prep...

Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias

Increased late sodium current in myocytes from a canine heart failure model and from failing human heart.

To investigate the role of the cytoskeleton in cardiac Na+ channel gating, the action of cytochalasin D (Cyto-D), an agent that interferes with actin polymerization, was studied by whole cell voltage clamp and cell-attached and inside-out patches from rat and rabbit ventricular cardiac myocytes. Cyto-D (20-40 microM) reduced whole cell peak Na+ current by 20% within 12 min and slowed current decay without affecting steady-state voltage-dependent availability or recovery from inactivation. Brief treatments ( 50% within 20 min, and long bursts of openings occurred. Washout of Cyto-D did not restore ensemble-averaged current amplitude, but burst duration decreased toward control values. Cyto-D also induced an additional slower component to open and closed times. These results suggest that Cyto-D, through effects on cytoskeleton, induced cardiac Na+ channels to enter a mode characterized by a lower peak open probability but a greater persistent activity as if the inactivation rate was slowed. The cytoskeleton, in addition to localizing integral membrane proteins, apparently also plays a role in regulating specific detailed functions of integral membrane proteins such as the gating of Na+ channels.

Cytoskeleton modulates gating of voltage-dependent sodium channel in heart

Single Na channels from rat and rabbit ventricular cells were studied with use of the excised inside-out patch-clamp technique. To investigate local anesthetic interactions with Na channels modified by the ischemic metabolite lysophosphatidylcholine (LPC), the quaternary ammonium lidocaine derivative QX-222 [2-(trimethylamino)-N-(2,6-dimethylphenyl)acetamide] was applied to the cytoplasmic side of patches from untreated cells and from those treated with LPC for approximately 1 h. Single-channel amplitudes and kinetics for unmodified channels were similar to those reported previously for cardiac cells with a single-component, mean-channel open time. LPC-modified channels showed prolonged open channel bursting with a two-component, mean open time, suggesting two open states. Conductance sublevels to the 60-70% level of the main conductance were found in both unmodified and LPC-modified channels and also with and without QX-222 present. QX-222 reversibly shortened the open time of the unmodified channel and for both open times of the LPC-modified channel without decreasing single-channel amplitude. Calculated association rates for QX-222 with the channel were found to be greater for the open states of the modified channel than those for the unmodified channel. Thus the lidocaine analogue QX-222 interacts with and blocks the open state of both unmodified and LPC-modified, cardiac Na channels. The blocking effect on LPC-modified channels would be predicted to be greater both because of the longer dwell time in the high-affinity open states for modified channels and also because of an intrinsically greater association rate in the modified channels.

J. C. Makielski

Papers

Cytoskeleton modulates gating of voltage-dependent sodium channel in heart

Blockade of lysophosphatidylcholine-modified cardiac Na channels by a lidocaine derivative QX-222.