TTXsensitive

TTXsensitive is a term used in neurophysiology and pharmacology to describe voltage-gated sodium channels (Nav) that are inhibited by tetrodotoxin (TTX) at nanomolar concentrations. Channels classified as TTXsensitive differ from those that require much higher, often micromolar, TTX levels to be blocked. The designation helps researchers distinguish which Nav isoforms contribute to fast neuronal signaling under TTX exposure.

TTX exerts its blocking action by binding to the outer pore of the sodium channel, near the selectivity filter, thereby preventing sodium ion flux and stopping action potential generation and propagation. Sensitivity to TTX is determined by specific amino-acid residues in the channel’s pore region and surrounding structures. In mammals, most neuronal Nav isoforms are TTXsensitive, while certain cardiac and peripheral channels show reduced sensitivity and are commonly described as TTX-resistant.

Common examples and implications: Nav1.1, Nav1.2, Nav1.3, Nav1.6, and Nav1.7 are typically categorized as TTXsensitive, whereas Nav1.5 (cardiac), Nav1.8, and Nav1.9 are often described as TTX-resistant. The TTX sensitivity profile of Nav channels is important for experimental design, allowing selective blockade of specific channels to study their roles in neural excitability, pain pathways, and cardiac conduction.

Applications and context: TTX is widely used as a research tool to parse the contributions of different Nav isoforms to neuronal signaling and to test pharmacological agents targeting specific channel subtypes. Variations in sensitivity across species and mutations in Nav genes can shift channels along the TTX sensitivity spectrum, informing evolutionary biology and toxin resistance studies. See also tetrodotoxin, voltage-gated sodium channel, and Nav channel subtypes.