Abstract: Provided herein a single-domain antibodies (sdAbs) that bind to voltage-gated sodium channel (Nav)1.4 or Nav1.5 and polynucleotides encoding the sdAb. Also provided herein are expression cassettes, vectors and host cells including polynucleotides N encoding the sdAb, and pharmaceutical composition including the sdAb, and methods of use thereof. The methods include the detection and/or capture Nav1.4 or Nav1.5 in a sample, the detection of a disease or condition in a subject, and the treatment of cardiac arrhythmia, myotonia, sudden cardiac death syndrome or cancer in a subject using sdAbs that bind Nav 1.4 or Nav 1.5.

Abstract: The method for increasing contractility in patients with systolic heart failure involves screening for candidate small molecules which block the interaction between Rad and the plasma membrane and/or block the interaction between Rad and the CaV1.2/CaV?2 complex, or between Rad and CaV?2, in order to increase cardiac contractility. A method for preventing calcium overload and arrhythmias in heart disease involves preventing the dissociation of Rad and the CaV1.2/CaV?2 complex, or between Rad and CaV?2, during beta-adrenergic system activation. Additionally, a method of screening for drugs that block interaction between an RGK GTPase protein and a ?-subunit of the calcium channel is provided. A suitable technique, such as fluorescence resonance energy transfer (FRET), may be used to assess blocking of the interaction between the RGK GTPase protein and the ?-subunit of the calcium channel for the treatment of heart disease, pain, diabetes, skeletal muscle disorders and/or central nervous system (CNS) disorders.