A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle.

The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe an in silico model, which we call the 'Hernandez-Hernandez model', of electrical and Ca signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca signaling during the development of myogenic tone in arterial blood vessels.

The formation of K2.1 macro-clusters is required for sex-specific differences in L-type Ca1.2 clustering and function in arterial myocytes.

In arterial myocytes, the canonical function of voltage-gated Ca1.2 and K2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively.

The formation of K 2.1 macro-clusters is required for sex-specific differences in L-type Ca 1.2 clustering and function in arterial myocytes.

In arterial myocytes, the canonical function of voltage-gated Ca 1.2 and K 2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively.

A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle.

The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe an model, which we call the "Hernandez-Hernandez model", of electrical and signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular signaling during the development of myogenic tone in arterial blood vessels.

Regulation of neuronal excitation-transcription coupling by Kv2.1-induced clustering of somatic L-type Ca channels at ER-PM junctions.

In mammalian brain neurons, membrane depolarization leads to voltage-gated Ca channel-mediated Ca influx that triggers diverse cellular responses, including gene expression, in a process termed excitation-transcription coupling. Neuronal L-type Ca channels, which have prominent populations on the soma and distal dendrites of hippocampal neurons, play a privileged role in excitation-transcription coupling. The voltage-gated K channel Kv2.

Kv2.1 channels play opposing roles in regulating membrane potential, Ca channel function, and myogenic tone in arterial smooth muscle.

The accepted role of the protein Kv2.1 in arterial smooth muscle cells is to form K channels in the sarcolemma. Opening of Kv2.