Lecture 5.1: Cellular Mechanisms Involved in Regulation of the Intracellular Concentration, and Cardiac Muscle Contraction

Question 1

What is Calcium’s Role in the Body? (3)

Answer 1

• Structural role in bone
• Linked with phosphate metabolism
• Many body functions depend on the intra-cellular
  fluid (ICF) and extra-cellular fluid (ECF) calcium levels
  e.g. hormone secretion, muscle contraction

Question 2

What processes is Calcium responsible for/does it regulate? (8)

Answer 2

• Fertilization
• Proliferation
• Secretion
• Neurotransmission
• Metabolism
• Contraction
• Learning and memory
• Apoptosis and necrosis

Question 3

The Physiochemical Forms of Plasma Calcium (3)

Answer 3

• Free ionised (Ca²⁺)- biologically active, 50% of total Ca²⁺
  plasma
• Bound to anionic sites on serum proteins (albumin),
  40% of total Ca²⁺ plasma
• Complexed with low molecular weight organic anions
  (e.g. phosphate, citrate), 10% of total Ca²⁺ plasma

Question 4

How Does Ca2+ Control Cellular Events?

Answer 4

• Trigger proteins mediate intracellular effects of
  calcium
• They bind Ca2+ which alters their conformation and
  function
• This triggers a cellular response

Question 5

Examples of Trigger Proteins (3)

Answer 5

• Synaptotagmin
• Calmodulin
• Troponin

Question 6

How Is the Ca2+ Gradient Set-up and Maintained?

Answer 6

• Relative Impermeability of the Plasma Membrane
• The Ability of Cell to Expel Ca2+ Across the Plasma
  Membrane
• Ca2+ Buffers
• Intracellular Ca2+ Stores

Question 7

How Is the Ca2+ Gradient Set-up and Maintained?: Relative Impermeability of the Plasma Membrane

Answer 7

Ca²⁺ ion channels are closed at resting membrane
potential

Question 8

How Is the Ca2+ Gradient Set-up and Maintained?: The Ability of Cell to Expel Ca2+ Across the Plasma Membrane

Answer 8

a) PMCA (Plasma Membrane Ca2+ ATPase
b) 3Na+/Ca2+ Exchanger (NCX) -activity dependent on
membrane potential

Question 9

Feedback Mechanism for PMCA

Answer 9

• [Ca2+]i increases
• Ca2+ binds to calmodulin
• (Ca2+-binding protein – a trigger protein)
• Ca2+-calmodulin binds and activates Ca2+-ATPase
• Ca2+-ATPase removes Ca2+

Question 10

The mode of operation of NCX is reversed when…?

Answer 10

The membrane is depolarised

Question 11

How Is the Ca2+ Gradient Set-up and Maintained?: What are Ca2+ Buffers?

Answer 11

• They are Ca2+- binding proteins
• Such as parvalbumin, calreticulin, calbindin and
  calsequestrin (ATP acts as Ca2+ buffer)

Question 12

How Is the Ca2+ Gradient Set-up and Maintained?: How do Ca2+ Buffers work?

Answer 12

• Ca2+ buffers limit Ca2+ diffusion
• Ca2+ diffusion depends on concentration of binding
  molecules and their level of saturation
• Decrease the intracellular Ca2+ concentration by
  binding excess Ca2+

Question 13

How Is the Ca2+ Gradient Set-up and Maintained?: Intracellular Ca2+ Stores (2)

Answer 13

• Rapidly releasable (sarcoplasmic and endoplasmic
  reticulum) [SERCA pump S/ER Ca2+ ATPase]
• Non-rapidly releasable (mitochondrion)

Question 14

How is the [Ca2+]i Elevated and Returned to Basal Levels? ()

Answer 14

• Ca2+ Influx Across the Plasma Membrane
• Ca2+ Release From Rapidly Releasable Intracellular
  Stores

Question 15

How is the [Ca2+]i Elevated and Returned to Basal Levels?: Ca2+ Influx Across the Plasma Membrane

Answer 15

Altered membrane permeability

Question 16

Ca2+ Influx Across the Plasma Membrane, what channels are responsible?

Answer 16

a) Voltage-operated Ca2+ channels (VOCC)
b) Receptor-Operated Ca2+ Channels (ROCC) (Ionotropic
or ligand-gated ion channels)

Question 17

How is the [Ca2+]i Elevated and Returned to Basal Levels?: