Function of BKCa channels is reduced in human vascular smooth muscle cells from Han Chinese patients with

Yan Yang1, Peng-Yun Li, Jun Cheng

  • 1Key Laboratory of Medical Electrophysiology, Ministry of Education of China, and the Institute of Cardiovascular Research, Luzhou Medical College, Luzhou, Sichuan, China.

Insights

Large-conductance Ca(2+)- and voltage-activated K(+) (BK(Ca)) channels show impaired function in hypertensive patients. Reduced BK(Ca) channel activity, specifically the β1-subunit, contributes to dysfunctional artery relaxation in hypertension.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Hypertension Research

Background:

  • Chronic hypertension is linked to impaired vascular relaxation and increased vascular tone.
  • The precise molecular mechanisms behind this vascular dysfunction in humans remain unclear.

Purpose of the Study:

  • To investigate the role of large-conductance Ca(2+)- and voltage-activated K(+) (BK(Ca)) channels in arterial relaxation dysfunction in Han Chinese patients with hypertension.
  • To examine the gene and protein expression of BK(Ca) channel subunits (α-subunit [KCa1.1] and β1-subunit [KCNMB1]) in vascular smooth muscle cells and mesenteric arteries.

Main Methods:

  • Utilized perforated patch clamp, inside-out single-channel, and macromembrane patch recording techniques.
  • Assessed whole-cell current, spontaneous transient outward current, open probability, and Ca(2+) sensitivity.
  • Employed reverse transcription polymerase chain reaction and Western blot analysis for gene and protein expression.

Main Results:

  • Vascular smooth muscle cells from hypertensive patients exhibited significantly decreased whole-cell current density, spontaneous transient outward current, and Ca(2+) sensitivity.
  • mRNA and protein levels of the KCNMB1 (β1-subunit) were reduced in arterial tissue from hypertensive patients, while KCa1.1 (α-subunit) levels were unchanged.
  • Single-channel open probability and slope conductance were not significantly different between groups.

Conclusions:

  • BK(Ca) channel function, including whole-cell current, spontaneous transient outward current, and Ca(2+) sensitivity, is reduced in human vascular smooth muscle cells from hypertensive patients.
  • This reduction is attributed to the downregulation of the BK(Ca) channel's β1-subunit (KCNMB1).
  • Downregulation of the β1-subunit of BK(Ca) channels may contribute to the impaired artery relaxation observed in Han Chinese patients with primary hypertension.

Related Concept Videos

Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
Antihypertensive Drugs: Action of β1 Blockers01:17

Antihypertensive Drugs: Action of β1 Blockers

β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this, β1-blockers...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
Antihypertensive Drugs: Types of β-Blockers01:28

Antihypertensive Drugs: Types of β-Blockers

β receptors are classified into three subclasses: β1, β2, and β3. β1 receptors are primarily located in the heart and kidneys. When they get activated, they increase heart rate, contractility, and renin release. This process enhances blood pressure and aids in stress management. In contrast, β2 receptors are situated mainly in the lungs, blood vessels, and skeletal muscles. Upon activation, they trigger smooth muscle relaxation, causing bronchodilation and vasodilation. This widens airways and...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...