Biophysical Basis of Physiology and Calcium Signaling Mechanism in Cardiac and Smooth Muscle

Tetsuya Watanabe

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128149515
• Topic: Sciences biologiques
• Subtopic: Biologie

Biophysical Basis of Physiology and Calcium Signaling Mechanism in Cardiac and Smooth Muscle acts as a bridge between physiology and physics by discussing the physiology and calcium signaling mechanism in cardiac and smooth muscle. By exploring the mechanism of the cyclic release of stored Ca^(2+) in the SR or ER, this book covers the cell communication system, including excitable cells, recognizing the most relevant mechanisms of cell communication. Serving as a bridge between physiology and physics, coverage spans the physiology and calcium signaling mechanism in cardiac and smooth muscle, offering insight to physiological scientists, pharmaceutical scientists, medical doctors, biologists and physicists.

• Explores the mechanism of the cyclic release of stored Ca^2+ in the SR or ER
• Provides in-depth coverage of cell communication systems to explain the most relevant mechanisms of cell communication
• Covers the physiology and calcium signaling mechanism in cardiac and smooth muscle

Chapter 1

Introduction

Abstract

Diffusion occurs wherever electric and concentration gradient exists, while flow may occur wherever pressure gradient exists. The speed of diffusion depends on temperature and the tissue property. The cyclic discharge of stored Ca^{2 +} from SR or ER was thought to be a basic source of cardiac and intestinal automaticity. It was considered as a natural diffusion phenomenon and evaluated mathematically using a model of Ca^{2 +} diffusion through the leaky channel. The movement of the cytosolic Ca^{2 +} level shows a damped harmonic oscillation along the straight line with a negative slope. The HCN channel is called the modulator of cardiac automaticity which may increase and stabilize frequency of action potential in the SA node pacemaker cells by means of the activation elicited from an adequate amount of cyclic AMP. In the intestine, inositol triphosphate (IP₃) modulates the discharge of Ca^{2 +} from the ER.

Keywords

Diffusion; Transporter; Funny currents; Automaticity; Ca^{2 +} oscillation; Na⁺-Ca^{2 +} exchanger; Stabilization of signal; Neuronal communication; Second messengers; Modulator of cardiac automaticity

1.1 Mixing, Dilution, and Diffusion

Mixing and dilution of molecules go spontaneously under constant temperature and pressure. These phenomena can be explained by diffusion. Diffusion is defined as the tendency of molecules or ions to move from its higher concentration area to its lower concentration area along the concentration gradient. The driving force of diffusion is the kinetic energy of molecules given by heat transfer. Continuous collisions among molecules produce the pressure fluctuation and bump them down from the area of a higher concentration along a jerky irregular path. And the greater the difference in concentration, the faster the net diffusion of the molecules becomes. Diffusion will stop when the concentration gradient becomes minimized. Increasing temperature results in faster diffusion by an increasing speed of molecules. If temperature and the concentration gradient are the same, the speed of diffusion depends on electrophysical property of the tissue fluid, the size of diffusible molecules, and viscosity of the fluid. Fick's law of diffusion can explain mixing and dilution of molecules mechanically and gives an idea of the speed of movements of particles toward equilibrium.

1.2 Diffusion Through Channels and Transporters

The cell membranes are made of phospholipids, cholesterol, and proteins. The phospholipid bilayer forms the basic structure of the membrane. This self-orienting property of phospholipids leads the biological membrane into a closed spherical structure and reseals it by itself when torn out. Only gases such as oxygen, carbon dioxide, and nitrogen and small nonpolar lipid soluble molecules can diffuse freely through the phospholipid bilayer membrane along their concentration gradients. Ions and polar molecules cannot diffuse through it. Ions and small polar molecules need channels or transporters which are made of columnar proteins firmly inserted into the phospholipid bilayer. Some channels have two states, open and closed, as seen in ligand-gated ion channels and the voltage-gated channels. Only the open state channels act as pores for the selected ions. On the other hand, a transporter forms an intermediate complex with the solute, and a subsequent conformational change in the transporter causes translocation of the solutes to the other side of the membrane. Passive transport processes require no energy supply. They are designed for diffusion of specified polar molecules such as glucose and amino acids that are too large to go through membrane channels by themselves. Active transport processes are used for ions to diffuse across cell membranes against the electrochemical gradients by means of energy supplied by ATP hydrolysis. Action of Na⁺-K⁺ pump is an important example of active transport. Since proteins cannot go through the membrane alone, the cell has a unique mechanism of production of the membrane and secreted proteins, and of their transports in the cell. Messenger RNA and ribosomes meet in the cytosol for translation. When the signal peptide is synthesized, the signal peptide on the ribosome is attached to the endoplasmic reticulum (ER) to complete translation, putting the growing peptide chain in the ER. Vesicles containing the proteins formed in the ER are transported to the Golgi apparatus where they are processed under glycosylation by adding, removing, or modifying glycans. Since every cell has a specific pattern of branching glycans on the surface of a cell, it provides a marker by which approaching cells recognize each other. From the Golgi, vesicles shuttle to the lysosomes or to the cell exterior via exocytosis. In exocytosis, cytoplasmic sides of two membranes fuse and then the area of fusion breaks releasing contents of the vesicle outside. Sudden influx of Ca^{2 +} into the cell needs to make the fusion possible. The cell membrane has many kinds of glycoproteins which give not only an extra mechanical strength to the membrane but also make the cell capable to communicate with the other cell.

1.3 Diffusion and Flow

Mixing and dilution of molecules go spontaneously under constant temperature and pressure. These phenomena can be explained by diffusion. Diffusion occurs wherever concentration gradient exists, while flow may occur wherever pressure gradient exists. Diffusion goes continuously in the direction to minimize the concentration gradient until equilibrium is achieved. The speed of diffusion depends on temperature, the size and charge of diffusible molecules, and the tissue property. Diffusion through channels or transporters is called facilitated diffusion. Because of low friction through channels, the flux is faster than that of simple diffusion. If the pressure gradient exists, flow may go in the direction to minimize the gradient until the equilibrium is achieved. The speed of flow does not depend on temperature but resistance of the passage. Magnitude of flow is proportional to pressure change and conversely proportional to resistance.

In the respiratory system when the gas flow stops, diffusion takes over the flow. Most of oxygen is carried as a form of oxyhemoglobin. At high altitudes, oxygen concentration in the blood plasma decreases but a total concentration of oxygen in blood is maintained almost constant since hemoglobin in the blood cell is almost saturated whenever the partial pressure of oxygen is above 70 mmHg. Since oxygen concentration is always higher in the blood of capillaries than in the tissue cells, it diffuses continuously to the cells via the interstitial fluid in one direction. Carbon dioxide is at higher concentrations in the tissue cells and so it diffuses in the opposite direction. The Fick's first law of diffusion is that flux per unit area is proportional to the concentration gradient and temperature, and conversely proportional to the friction of the molecule in the tissue. Fick's principle has been applied to measure cardiac output and cerebral blood flow. The concentration gradient of gases or small nonpolar lipid-soluble molecules in the membrane is mathematically justified. It was found to be linear in the membrane if the concentrations of the both sides of membrane are maintained at different constant values. Pressure difference between the atmospheric pressure and alveoli per air flow through trachea gives the airway resistance. The pressure changes in the air-tight body plethysmograph with a patient sitting in give the alveolar pressure change in the lungs after correlation, which makes the measurement of the airway resistance possible without a cannulation in human.

1.4 Diffusion and Currents

Ions diffuse according to electrochemical gradient through the ion channels in the membrane. Ion diffusion through the membrane causes currents, which can change the electrical potential inside the cell. The channels are made of columnar proteins, and their open and close states are controlled by bonding of the ligand to the receptor on the ion channel protein or by means of the voltage sensor. On the other hand, their open and close states at gap junction in ventricular myocardium and smooth muscle are controlled by connexin 43 phosphoryla...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Acknowledgments
• Chapter 1: Introduction
• Chapter 2: Statistical Thermodynamics
• Chapter 3: Shielding Effect and Chemical Bonding
• Chapter 4: The Cell
• Chapter 5: Diffusion and Flow, and Respiratory System
• Chapter 6: Peripheral Nervous Systems
• Chapter 7: Calcium Signaling in the Heart and Small Intestine
• Chapter 8: Mechanism of Cardiac Arrhythmias and Antiarrhythmic Drugs
• Reference Data
• Index