Principles of Physiology for the Anaesthetist

Peter Kam, Ian Power

• Publisher: CRC Press
• Year: 2015
• ISBN:
  9780429585845
• Edition: 3
• Topic: Médecine
• Subtopic: Théorie, pratique et référence de la médecine

Principles of Physiology for the Anaesthetist, now in its Third Edition, continues to provide candidates with a "tailor-made" alternative to more general physiology textbooks and delivers information designed and written specifically with the trainee anaesthetist in mind. The book covers the physiology of all major organ systems, with specific emph

1

Physiology of excitable cells

LEARNING OBJECTIVES

After studying this chapter, the reader should be able to

1. Describe the nature of the cell membrane and the ionic basis of the resting membrane potential.

2. Describe the nerve action potentials in nerves, cardiac cells and muscle cells.

3. Describe the propagated action potential.

4. Understand ion channels that are voltage gated: sodium, potassium and calcium channels.

5. Describe neurotransmitters and receptors, including ion channels, G proteins and second messengers.

6. Understand the structure and function of the specialized connection between nerves and striated muscle (the neuromuscular junction), with comprehension of the mechanism of neuromuscular transmission.

7. Understand the different structures of skeletal, cardiac and smooth muscles.

8. Describe the role of muscle spindles, Golgi tendon organs and spinal reflexes.

9. Understand the classification and mechanisms of activation of sensory receptors, including those for pain.

INTRODUCTION

An excitable cell responds to a stimulus by a rapid change in the electrical charge of the cell membrane. Nerve, muscle and sensory cells can be included in this classification, as the excitability of these tissues lies in the changing electrical properties of their membranes.

This chapter examines the physiology of some excitable cells. First, the structure of the cell membrane and the ionic basis for the resting membrane potential are examined, followed by the form of action potential for both nerves and muscle. Next, voltage-sensitive membrane ion channels are described and their role in the action potential is discussed. In the section ‘Membrane potential’, chemical communication between excitable cells is examined, by investigating the interaction of receptors, ion channels, G proteins and intracellular messengers. The physiology of neuro-muscular transmission is then presented, followed by a discussion of skeletal, cardiac and smooth muscle cells, together with details of contractile proteins, the mechanical response to stimulation and excitation–contraction coupling. In the section ‘Membrane potential’, organs involved in the regulation of muscle movement, muscle spindles and tendon organs are discussed, together with an examination of stretch reflexes. Finally, sensory receptors are classified and their physiology is described.

MEMBRANE POTENTIAL

Cell membrane

Cell membranes (Figure 1.1) are bilayers of phospholipids with polar heads to the outside and Physiology of excitable cells lipophilic fatty tails to the inside. This structure separates the cellular contents and the cytoplasm from the extracellular fluid. Integral proteins traverse the membrane, whereas peripheral proteins sit on the cytoplasmic and extracellular surfaces. Peripheral proteins on the inside and outside have different functions; glycoproteins have their sugar residues on the outside, and transporting enzymes bind adenosine triphosphate (ATP) on the inside.

The cell membrane can be thought of as a layer of insulation covered on both sides by conducting material. This structure is traversed by protein channels that determine ionic permeability and the resultant electrical potential across the membrane.

RESTING MEMBRANE POTENTIAL

Cell membranes have an electrical charge across them with the inside being 70–80 mV negative with respect to the outside (Figure 1.2). This electrical potential depends on two main factors: the selective membrane permeability to ions and the different ionic concentrations on the inside and outside of the cell. The former is the more important factor, as it can change. At rest, most membranes are permeable to potassium but not sodium ions. Membranes can be described as being semipermeable to ions; potassium passes across them with ease, but most others do not (Figure 1.3).

The potassium concentration is much higher inside (150 mM) than outside (5 mM) the cell. Potassium diffuses down this concentration gradient out of the cell, but this movement cannot continue indefinitely as it is opposed by electrical forces. As the membrane is impermeable to other cations, the movement out by positively charged potassium ions produces a negative charge on the inside of the cell. This charge tends to oppose and prevent further movement of potassium out of the cell. Therefore, there are opposing chemical and electrical gradients acting on potassium ions (chemical: out; electrical: in). At the resting membrane potential of around −70 mV, the electrical and chemical gradients acting on potassium ions balance. That is, the resting membrane potential is due to the equilibrium of the electrochemical gradients affecting potassium ions (Figure 1.4).

The Na⁺ –K⁺ pump, which transports three sodium ions to the outside for every two potassium ions pumped inside, causes a continual loss of positive ions from inside the membrane and therefore is electrogenic because it produces a net deficit of positive charges inside the cell. This causes an additional negative charge of about −4 mV inside the cell membrane.

Figure 1.1 Diagrammatic representation of the cell membrane.

Figure 1.2 The resting membrane potential.

Figure 1.3 Membrane permeability to sodium and potassium ions. (The chemical symbol size indicates the relative ionic concentrations of K⁺ and Na⁺.)

It is important to realize that only a small number of potassium ions have to move to produce the resting potential. For a membrane potential of −70 mV, the difference between the numbers of positive and negative charges inside the cell is only 0.000002%.

Proteins are the main intracellular anions, but they also have little effect as they cannot traverse the membrane. The primary extracellular ion – chloride – can pass freely across the membrane (Figure 1.5), but the resultant potential is similar to that set up by potassium. This can be demonstrated by considering the electrochemical forces on chloride ions.

Figure 1.4 Equilibration of potassium ions across the cell membrane – the electrochemical gradient. At the equilibrium potential for potassium, the chemical and electrical gradients are in balance. Δc, chemical gradient; Δe, electrical gradient.

Figure 1.5 Passage of chloride ions across the cell membrane.

Other cations – sodium included – contribute relatively little to the resting potential as the membrane is quite impermeable to them. If the membrane was permeable to sodium, then the potential would be completely reversed as the electrochemical gradient is opposite to that of potassium (Figure 1.6).

Figure 1.6 Passage of sodium ions across the cell membrane.

Nernst equation

The Nernst equation calculates the potential difference that any ion would produce if the membrane was permeable to it...