Synthetic ion channels represent a new approach to mimicking natural ion channels and developing therapeutic drugs to restore ion channel dysfunction. The large superfamily of transient receptor potential (TRP) channels involved in numerous biological processes is an important and potent therapeutic target for various human diseases. In the present study, a synthetic peptide whose sequence is from the fourth transmembrane segment of TRPV4 is found that is capable of self-assembling into potassium (K⁺)-like ion channels designated as TRP-PK1 in the membranes of liposomes and live cells. TRP-PK1 effectively mediates K⁺ flow across the cell membrane to regulate the membrane potential. TRP-PK1 is also able to relax agonist-induced vessel contraction and regulate the resting blood pressure by hyperpolarizing the vascular smooth muscle cell membrane potential. TRP-PK1 represents a novel lead compound for mimicking K⁺ channels and treating hypertension, heart rate disorder and other K⁺ channel dysfunction-induced diseases. The present study also sheds new light onto the mimic ion channel function and the significant utilization of natural biological sources.