How do inward rectifying potassium (K) channels contribute to the determination of the resting membrane potential in cardiac cells?

From the Guidelines

Inward rectifying potassium (Kir) channels are crucial for determining the resting membrane potential of cardiac cells by allowing potassium ions to flow more easily into the cell than out of it, which is essential for maintaining normal cardiac electrical activity. While many potassium channels primarily allow potassium to exit the cell, Kir channels function differently due to their unique property of rectification. At negative membrane potentials (during rest), Kir channels permit potassium influx, which helps maintain the resting potential close to the potassium equilibrium potential (around -90 mV) 1. As the membrane potential becomes more positive during depolarization, these channels exhibit "rectification" - they become blocked by intracellular magnesium ions and polyamines, reducing potassium efflux.

Key Mechanisms

• Kir channels allow potassium ions to flow into the cell at negative membrane potentials, helping to maintain the resting potential
• The channels exhibit rectification, becoming blocked by intracellular magnesium ions and polyamines as the membrane potential becomes more positive
• This unique property helps prolong the cardiac action potential plateau phase and prevents premature repolarization

Importance in Cardiac Function

The mechanism of Kir channels is essential for normal cardiac electrical activity, as it stabilizes the resting potential and contributes to the characteristic shape of the cardiac action potential. Understanding the regulation and modulation of ion channels, including Kir channels, is critical for determining how they are regulated in the native environment and constructing a complete picture of electromechanical functioning in the human heart 1.

Regulation and Modulation

Ion channels in the heart, including Kir channels, are targets of multiple modifications that permit normal cardiac function, drive or suppress disease states, and induce or respond to processes like aging 1. The regulation of ion channels occurs on many temporal and spatial scales, resulting in targeting of channels to specific membrane locations and subsequent regulation by second messengers, hormones, neurotransmitters, humoral factors, kinases, phosphatases, and structural modulation by subsidiary subunits. Improving our understanding of the regulation of ion channels is a critical future research direction, and the collection of electrophysiological data, protein levels, and mRNA in cardiocytes derived from humans across the spectrum of age and disease states is a primary recommendation for improving our understanding of ion channel regulation 1.

From the Research

Inward Rectifying K Channels and Resting Potential

• Inward rectifying K channels, specifically the cardiac inwardly rectifying potassium channel (I(K1)), play a crucial role in determining the resting potential of the heart 2, 3, 4.
• These channels are characterized by their ability to conduct larger inward currents than outward currents, resulting in an inwardly rectifying current versus voltage relationship 5, 6.
• The inward rectification property of these channels allows them to maintain the resting potential near the K+ equilibrium potential (EK) 5.

Mechanism of Inward Rectification

• The mechanism of inward rectification is due to the voltage-dependent block of the channels by intracellular polyvalent cations 5, 6.
• This blockage prevents outward K+ currents, while allowing inward K+ currents to flow, thereby maintaining the resting potential 5, 6.

Role of I(K1) in Cardiac Excitability

• I(K1) is highly influential on the resting potential and plays a significant role in cardiac excitability and arrhythmogenesis 2, 3.
• Modulation of I(K1) can have profound effects on cardiac excitability and arrhythmogenesis, and may be a potential target for antiarrhythmic therapy 2, 3.

Direction of K+ Movement

• Although K channels typically allow K+ to move out of the cell, inward rectifying K channels allow K+ to move into the cell, which helps to maintain the resting potential 5, 6.
• The unique property of inward rectification in these channels enables them to conduct inward K+ currents, which is essential for maintaining the resting potential of the heart 5, 6.