RESUMO
Effective pump function of the heart depends on the precise control of spatial and temporal patterns of electrical activation. Accordingly, the distribution and function of gap junction channels are important determinants of the conduction properties of myocardium and undoubtedly play other roles in intercellular communication crucial to normal cardiac function. Recent advances have begun to elucidate mechanisms by which the heart regulates intercellular electrical coupling at gap junctions in response to stress or injury. Although responses to increased load or injury are generally adaptive in nature, remodeling of intercellular junctions under conditions of severe stress creates anatomic substrates conducive to the development of lethal ventricular arrhythmias. Potential mechanisms controlling the level of intercellular communication in the heart include regulation of connexin turnover dynamics and phosphorylation.
Assuntos
Cardiomegalia/metabolismo , Comunicação Celular/fisiologia , Conexinas/metabolismo , Junções Comunicantes/metabolismo , Insuficiência Cardíaca/metabolismo , Doença Aguda , Arritmias Cardíacas/metabolismo , Doença Crônica , Condutividade Elétrica , Humanos , FosforilaçãoRESUMO
Gap junctions contain channels which allow the exchange of ions and small molecules between adjacent cells. In the heart, these channels are crucial for normal intercellular current flow and the propagation of action potentials throughout the myocardium. Molecular cloning studies have demonstrated that these channels are formed by members of a family of related proteins called connexins each containing conserved and unique regions. There are several consequences of this multiplicity of connexins. Multiple connexins are expressed in differing, but sometimes overlapping, distributions within cardiovascular and other tissues. Connexin40, connexin43, and connexin45 are all found in cardiac myocytes, but their abundance differs in specialized cardiac regions with disparate conductive properties. Individual connexins form channels with differing voltage-dependence, conductance, and permeability properties, as demonstrated by functional expression of the cloned sequences. Connexins differ in their modification by phosphorylation, which may contribute to physiological regulation of intercellular communication. Expression of multiple connexins may lead to the formation of multiple channel types in a single tissue or cell and potentially allows mixing to form heterotypic and/or heteromeric channels. Thus, multiple connexins may contribute to the differences in intercellular resistance in cardiac regions with differing conductive properties and possibly may allow differences in the signalling molecules that pass between cells.