Vascular smooth muscle ion channels in essential hypertension

Abstract

Hypertension is a highly prevalent chronic disease and the major risk factor for cardiovascular diseases, the leading cause of death worldwide. Hypertension is characterized by an increased vascular tone determined by the contractile state of vascular smooth muscle cells that depends on intracellular calcium levels. The interplay of ion channels determine VSMCs membrane potential and thus intracellular calcium that controls the degree of contraction, vascular tone and blood pressure. Changes in ion channels expression and function have been linked to hypertension, but the mechanisms and molecular entities involved are not completely clear. Furthermore, the literature shows discrepancies regarding the contribution of different ion channels to hypertension probably due to differences both in the vascular preparation and in the model of hypertension employed. Animal models are essential to study this multifactorial disease but it is also critical to know their characteristics to interpret properly the results obtained. In this review we summarize previous studies, using the hypertensive mouse (BPH) and its normotensive control (BPN), focused on the identified changes in the expression and function of different families of ion channels. We will focus on L-type voltage-dependent Ca2+ channels (Cav1.2), canonical transient receptor potential channels and four different classes of K+ channels: voltage-activated (Kv), large conductance Ca2+-activated (BK), inward rectifiers (Kir) and ATP-sensitive (KATP) K+ channels. We will describe the role of these channels in hypertension and we will discuss the importance of integrating individual changes in a global context to understand the complex interplay of ion channels in hypertension.

Impairment of exocytotic transmitter release by decynium-22 through an inhibition of ion channels

“…D22, in contrast, led to an unexpected drop in blood pressure, and this was due to antagonistic actions at α 1 adrenergic receptors ( Russ et al, 1996 ). In this context, one should not forget that blockers of Cav1 channels lead to a reduction of blood pressure as well ( Daghbouche-Rubio et al, 2022 ). Moreover, cocaine’s psychostimulant activity causes hyperlocomotion ( Uhl et al, 2002 ), whereas D22 is known to reduce locomotor activity by a yet unidentified mechanism ( Krause-Heuer et al, 2017 ).…”

Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: The Role of the Membrane Potential and Ion Channels

“…Various types of ion channels play crucial roles in regulating membrane potential and intracellular Ca 2+ concentration in smooth muscle cells. Notably, the differential expression patterns of ion channels and their regulation by signaling pathways can lead to distinct contractile or relaxant responses, influencing muscle tone and contraction [ 73 ]. These channels, embedded within the sarcolemma, control the flow of ions across the cell membrane, influencing membrane potential and intracellular Ca 2+ concentrations, which are critical determinants of muscle contraction [ 21 ].…”

Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: Role of the Membrane Potential and Ion Channels

“…Various types of ion channels play crucial roles in regulating membrane potential and intracellular Ca 2+ concentration in smooth muscle cells. Notably, the differential expression patterns of ion channels and their regulation by signaling pathways can lead to distinct contractile or relaxant responses, influencing muscle tone and contraction [62]. These channels, embedded within the sarcolemma, control the flow of ions across the cell membrane, influencing membrane potential and intracellular Ca 2+ concentrations, which are critical determinants of muscle contraction [16].…”